NFL Week 5 game picks, schedule guide, fantasy football tips, odds, injuries and more

The Week 5 NFL schedule for the 2021 season is stacked with great matchups, and we got you covered with what you need to know heading into the weekend. Our NFL Nation reporters bring us the biggest keys to every game, a bold prediction for each matchup and, of course, final score picks.

Additionally, ESPN Stats & Information provides a big stat to know for each contest, and our Football Power Index (FPI) goes inside the numbers with a matchup rating (on a scale of 1 to 100) and a game projection. ESPN researcher Kyle Soppe hands out helpful fantasy football and betting nuggets as well. Everything you want to know is here in one spot to help you get ready for a loaded weekend of NFL football.

Let's get into the full Week 5 slate, including the first international game of the season, a big Justin Herbert-Baker Mayfield showdown, a tough test for Kyler Murray against the Niners' defense and, of course, a great matchup between the Bills and Chiefs on Sunday night. It all culminates with a Monday Night Football matchup between the Colts and the Ravens on ESPN. (Game times are Sunday unless otherwise noted.)

Jump to a matchup:

Thursday: LAR 26, SEA 17

Jets (1-3) vs. Falcons (1-3) (London)

9:30 a.m. ET | NFL Network
Matchup rating:
10.6 | Spread: ATL -2.5 (45)

What to watch for: According to the Elias Sports Bureau, this is the first time ever that two interception-less teams have met this late in the season. Atlanta dropped multiple near-interceptions last week, and Falcons defensive coordinator Dean Pees said he needs his defensive backs to be attacking the ball more. Jets quarterback Zach Wilson leads the NFL with eight interceptions, while Atlanta's Matt Ryan has three, so perhaps this is the week that at least one of these teams gets a big takeaway through the air. -- Michael Rothstein

Bold prediction: Rookie running back Michael Carter will deliver the Jets' first 100-yard rushing day of the season. The Jets will approach this game with a ball-control mindset, hoping to give the defense a break. The defense was on the field for 93 plays last week, the fourth-highest amount in an NFL game since 2000. The unit was gassed, and a cross-Atlantic trip to London didn't help. Enter Carter, who will have a breakout game. -- Rich Cimini

Stat to know: Ryan's average pass has traveled 5.9 air yards, the lowest in NFL this season. He is 2-of-8 on passes of at least 20 yards downfield and will be without No. 1 receiver Calvin Ridley on Sunday.

Injuries: Jets | Falcons

What to know for fantasy: Falcons running back Cordarrelle Patterson has been a top-20 back in each of the past three weeks, including a pair of top-five finishes at the position. See Week 5 rankings.

Betting nugget: Favorites in London games are 17-11 against the spread (ATS). But Atlanta -- the favorite in this one -- is 1-5 outright and ATS as a favorite since the start of last season. Read more.

Cimini's pick: Jets 24, Falcons 17
Rothstein's pick: Jets 24, Falcons 20
FPI prediction: ATL, 56.8% (by an average of 2.4 points)

Matchup must-reads: Jets linebacker Mosley: Tackling machine with a 'cheat code' ... Ridley won't travel to London for game with Jets for personal reasons ... Jets safety Maye facing charges from DUI arrest in February ... Jets make sack history

Dolphins (1-3) at Buccaneers (3-1)

1 p.m. ET | CBS
Matchup rating:
58.2 | Spread: TB -10 (48)

What to watch for: The Bucs' pass rush finally got things going last week in an emotional win over the Patriots. They can build off that against a Dolphins' offensive line that has surrendered 13 sacks so far this season -- fourth-most in the NFL -- and in turn protect a very vulnerable secondary that may be without all three starting cornerbacks and safety Antoine Winfield Jr. -- Jenna Laine

Bold prediction: In presumably his final start before Tua Tagovailoa returns, Dolphins quarterback Jacoby Brissett will leave it all on the field. He will throw two interceptions as a result of more aggressive decision-making, but he also will find the end zone three times on Sunday. -- Marcel Louis-Jacques

Stat to know: With his tight end Rob Gronkowski (ribs) out, Buccaneers quarterback Tom Brady went 2-of-8 for 29 yards with a 50% off-target percentage when throwing to tight ends against the Patriots. He has not thrown a touchdown to a tight end outside of Gronkowski since Week 10 of last season (Cameron Brate).

Injuries: Dolphins | Buccaneers

What to know for fantasy: Dolphins tight end Mike Gesicki has 35.3 points in Brissett's two starts this season and 7.1 in Tagovailoa' s two starts. It's Brissett's job for at least one more week, and it figures to be a pass-heavy game script. See Week 5 rankings.

Betting nugget: Since the start of last season, Miami is 6-1 ATS following a straight-up loss and 5-1 ATS as a road underdog. Read more.

Louis-Jacques' pick: Buccaneers 31, Dolphins 24
Laine's pick: Buccaneers 27, Dolphins 24
FPI prediction: TB, 74.9% (by an average of 9.2 points)

Matchup must-reads: Hand injury lands Dolphins receiver Fuller on IR ... With Bucs' Brady becoming the all-time pass leader, who's next? ... First fix for Miami's offense? Get Parker the ball

Saints (2-2) at Washington (2-2)

1 p.m. ET | CBS
Matchup rating:
53.3 | Spread: NO -2 (43.5)

What to watch for: How will Washington's defense attack the Saints' running back Alvin Kamara? Washington's linebackers have not played well and will be challenged by an offense that ranks seventh in the NFL with 132.8 rushing yards per game, led by Kamara with 209 yards combined over the past two weeks. Washington ranks 11th in yards per carry allowed and 17th in rushing yards per game, so it will need to force New Orleans quarterback Jameis Winston to beat it. -- John Keim

Bold prediction: The Saints' defense will make a statement after last week's uncharacteristic collapse against the Giants. They'll limit Washington to less than 50 rushing yards and force at least two interceptions, just like they did in wins over Green Bay and New England in Weeks 1 and 3. -- Mike Triplett

Stat to know: Washington quarterback Taylor Heinicke has multiple passing touchdowns in each of his first three regular-season starts with Washington. The only QB in team history to throw multiple TDs in four straight games over past 15 seasons is Kirk Cousins (twice).

Injuries: Saints | Washington

What to know for fantasy: Washington receiver Terry McLaurin set a career-high with 27.7 points in Week 2 and then topped it on Sunday in Atlanta with 30.3. See Week 5 rankings.

Betting nugget: After seeing the under hit in six straight games, the over has now hit in back-to-back-to-back Washington games. Read more.

Triplett's pick: Saints 24, Washington 16
Keim's pick: Saints 21, Washington 17
FPI prediction: NO, 57.0% (by an average of 2.5 points)

Matchup must-reads: Saints' Superdome homecoming ends with 4th-quarter flop ... Washington tight end Thomas expected to miss four weeks ... Is 26 rushes and zero targets the new normal for Kamara? ... Heinicke's magical moments carrying Washington

Packers (3-1) at Bengals (3-1)

1 p.m. ET | FOX
Matchup rating:
52.1 | Spread: GB -3 (50.5)

What to watch for: The Bengals are looking for their first three-game winning streak since 2018 and are facing the toughest test to date this season. Meanwhile, the Packers are dealing with several key injuries. Green Bay finished its Week 4 win over Pittsburgh without seven starters. -- Ben Baby

Bold prediction: Packers quarterback Aaron Rodgers will throw a rare pick-six. It has happened only three times in his career, but one of them came in the last meeting with the Bengals. Weird things seem to happen when the Packers play in Cincy. There was the 2005 game when a fan ran onto the field and snatched the ball out of Brett Favre's hands to stall a potential game-winning drive, and then there was the Jonathan Franklin fumble that the Bengals returned for the game-winning touchdown in 2013. This one won't cost the Packers the game, but it will make it close. -- Rob Demovsky

Stat to know: Green Bay receiver Davante Adams' 31 receptions lead the NFL and are his most through four games in his career. He also has 16 straight games with at least five catches, the longest active streak in the NFL and longest by a Packer since Sterling Sharpe (18 straight from 1993-94).

Injuries: Packers | Bengals

What to know for fantasy: One active player had a 30-yard catch in each of his first four career games: Bengals receiver Ja'Marr Chase. Since 2013, Stefon Diggs (2015) is the only player to rattle off five straight games with such a catch at any point during his rookie season. See Week 5 rankings.

Betting nugget: The Bengals are 7-4 ATS in their past 11 games as a home underdog. Read more.

Demovsky's pick: Packers 31, Bengals 28
Baby's pick: Bengals 27, Packers 24
FPI prediction: GB, 53.6% (by an average of 1.3 points)

Matchup must-reads: If Smith is another Campbell, then Packers' D got better ... Mixon day-to-day with ankle sprain, Taylor says ... Packers' salary-cap situation, not trade offer, prevented Gilmore move ... How 'Jeopardy!'-like review sessions are helping Burrow thrive

Broncos (3-1) at Steelers (1-3)

1 p.m. ET | FOX
Matchup rating:
49.2 | Spread: NL (40)

What to watch for: This game will be all about the battle up front, and edge rushers Von Miller (Broncos) and T.J. Watt (Steelers) against the offensive lines. The team that can generate the most pressure on the quarterback and force the most turnovers will come out ahead in this one. The Steelers' defense hasn't lived up to its Week 1 performance against the Bills, but this could be a get-right game against an undermanned Broncos' offense -- if they can slow down Denver running back Javonte Williams. -- Brooke Pryor

Bold prediction: Steelers quarterback Ben Roethlisberger may be trying to get rid of the ball as fast as possible -- he has three games this season with an average yards per attempt under 6 yards, and running back Najee Harris, at just under 7 yards per catch is the team's leading receiver -- but the Broncos will still sack him at least five times. And if they can consistently generate pressure in between the sacks, they should get their first road win in Pittsburgh since 2006. -- Jeff Legwold

Stat to know: Denver receiver Courtland Sutton has an average target depth of 17.4 yards downfield this season, the second-highest distance in the NFL behind Henry Ruggs III (17.5).

Injuries: Broncos | Steelers

What to know for fantasy: Denver tight end Noah Fant has three weeks with over 12 fantasy points. See Week 5 rankings.

Betting nugget: Pittsburgh and Denver are two of only four NFL teams to go under the total in every game this season. Read more.

Legwold's pick: Broncos 23, Steelers 19
Pryor's pick: Steelers 17, Broncos 14
FPI prediction: PIT, 50.6% (by an average of 0.3 points)

Matchup must-reads: Bridgewater leads list of nine Broncos' starters to suffer injury so far ... Steelers QB Roethlisberger notes hip pain but 'I need to be better' ... Lock's readiness to be tested if Broncos' Bridgewater misses time ... Tomlin says Roethlisberger 'absolutely' is best QB to run Steelers' offense

Eagles (1-3) at Panthers (3-1)

1 p.m. ET | FOX
Matchup rating:
45.3 | Spread: CAR -3 (45.5)

What to watch for: Carolina's offensive line is banged up with starting left tackle Cameron Erving (neck) not expected to play and left guard Pat Elflein still on IR with a hamstring injury. Trent Scott or rookie Brady Christensen could start for Erving, and coach Matt Rhule hasn't ruled out moving right tackle Taylor Moton to the left side. With running back Christian McCaffrey (hamstring) possibly returning, how the line performs against the NFL's 31st-ranked defense against the run is key. -- David Newton

Bold prediction: Panthers QB Sam Darnold's carriage will turn back into a pumpkin. It's been quite the Cinderella start for Darnold, who has three games with 300-plus passing yards this season and multiple rushing touchdowns each of the past two games. But his offensive line has been shaky even before the injuries. Carolina ranks 30th with a pass block win rate of 44%, and Darnold has been sacked 11 times, tied for sixth-most. Eagles defensive coordinator Jonathan Gannon and defensive tackle Fletcher Cox have faced sharp criticism after yielding over 850 yards the past two weeks, and each will come with an edge. Darnold will be roughed up and commit multiple turnovers. -- Tim McManus

Stat to know: Panthers receiver DJ Moore has 398 receiving yards this season, which is third-most through the team's first four games of the season in Panthers history.

Injuries: Eagles | Panthers

What to know for fantasy: Darnold has gone over 25 points in consecutive games, while Philadelphia's Jalen Hurts has been a top-11 quarterback every week this season. See Week 5 rankings.

Betting nugget: The Eagles are just 6-12 (both outright and ATS) over their past 18 road games. Read more.

McManus' pick: Eagles 26, Panthers 23
Newton's pick: Panthers 28, Eagles 23
FPI prediction: CAR, 64.7% (by an average of 5.2 points)

Matchup must-reads: Hurts' budding chemistry with Smith provides Eagles with hope ... Acquiring Gilmore from Patriots shows Panthers believe future is now

Lions (0-4) at Vikings (1-3)

1 p.m. ET | FOX
Matchup rating:
39.5 | Spread: MIN -9.5 (39.5)

What to watch for: Minnesota quarterback Kirk Cousins has dominated the Lions as a member of the Vikings, having thrown 15 touchdowns and one interception since 2018, and Minnesota is in the midst of a seven-game win streak over its divisional foe with an average margin of victory of 11.6 points per game. It won't get easier this week for the Lions. Detroit's offensive line will be shorthanded against Minnesota's stout pass rush (3.2 sacks per game, tied for third in the NFL). Center Frank Ragnow (toe) was placed on injured reserve this week, and the Lions are also preparing to play without left tackle Penei Sewell (ankle). -- Courtney Cronin

Bold prediction: Lions rookie wide receiver Amon-Ra St. Brown will make at least five catches. He had a breakout performance against Chicago last week, catching a game-high six passes for 70 yards -- both career-highs. Look for quarterback Jared Goff to try to connect with the receivers more to open up the potential of the offense, and St. Brown should get targeted more after proving he could make plays on the road. -- Eric Woodyard

Stat to know: Yes, Vikings running back Dalvin Cook had just 34 rushing yards in a Week 4 loss to the Browns, his fewest in a game since 2019. But he had a career-high 206 in his last meeting with the Lions (Week 9 last season) and has averaged 106.3 rushing yards per game -- and scored six TDs on the ground -- in six career games against Detroit.

Injuries: Lions | Vikings

What to know for fantasy: Cousins has scored more than 20 fantasy points in four of his past five games against the Lions. See Week 5 rankings.

Betting nugget: The over hit in five of Minnesota's six divisional games last season, including both matchups with Detroit. Read more.

Woodyard's pick: Vikings 28, Lions 23
Cronin's pick: Vikings 30, Lions 21
FPI prediction: MIN, 73.8% (by an average of 8.8 points)

Matchup must-reads: Goff, Lions trying not to 'go numb' to losing ... Vikings RB Cook vows to play through ankle injury ... Lions lose top pass-rusher Okwara for season ... Why isn't the Vikings' spending on rush defense paying off?

Patriots (1-3) at Texans (1-3)

1 p.m. ET | CBS
Matchup rating:
22.4 | Spread: NE -9 (39.5)

What to watch for: Will the Texans' run game show any improvement? The Patriots are ranked 28th in Football Outsiders' DVOA against the run, but can Houston take advantage? The team ranks 30th in rush DVOA so far and has gone downhill since Mark Ingram II ran for 85 yards and a touchdown in Week 1. -- Sarah Barshop

Bold prediction: The Patriots will rush for 200 yards as a team, with running back Damien Harris leading the way by eclipsing the 100-yard mark and scoring 2 TDs. The Texans rank 28th in the NFL in rushing yards allowed per game, and the Patriots are determined to get their ground game going after totaling minus-1 yard on 8 carries in last Sunday's loss to the Buccaneers. -- Mike Reiss

Stat to know: Houston QB Davis Mills posted a 0.8 Total QBR against the Bills in a Week 4 shutout, the fourth lowest in the past five seasons. He'd join Case Keenum as the only Texans players to lose their first three career starts with a loss on Sunday.

Injuries: Patriots | Texans

What to know for fantasy: Patriots receiver Jakobi Meyers has 42 targets this season -- tied for fifth most in the NFL -- and two straight games with 15-plus fantasy points. The last Patriots receiver with three straight 15-plus-point games was Julian Edelman from Week 12 to Week 14 in 2019. See Week 5 rankings.

Betting nugget: New England is 57-31 ATS following a straight-up loss under coach Bill Belichick. Read more.

Reiss' pick: Patriots 23, Texans 17
Barshop's pick: Patriots 17, Texans 7
FPI prediction: NE, 68.8% (by an average of 6.8 points)

Matchup must-reads: Why the Patriots traded Gilmore to Carolina ... Texans' franchise-worst loss to Bills 'embarrassing' ... LB Collins returns for third stint with Patriots

Titans (2-2) at Jaguars (0-4)

1 p.m. ET | CBS
Matchup rating:
21.0 | Spread: TEN -4.5 (49)

What to watch for: This game is all about getting Derrick Henry going -- and trying to stop him. In the first game these two teams play each year over the past three seasons, Henry has rushed for 185 yards and one touchdown. In the rematch, he has rushed for 612 yards and eight touchdowns. That doesn't mean Henry won't go off on Sunday, but the Jaguars do rank fifth defensively in the NFL in yards per carry allowed (3.7). -- Mike DiRocco

Bold prediction: The Titans won't allow a sack against the Jaguars. That's saying a lot, despite Jacksonville only have five sacks this season -- the Titans have allowed a league-high 17. The blame has been placed on receivers not getting open, quarterback Ryan Tannehill holding on to the ball too long and offensive linemen getting beat up front. Two things can help solve those issues: the possible return of receiver A.J. Brown and offensive coordinator Todd Downing going to more bunch formations to create separation and allow Tannehill to get rid of the ball more quickly. -- Turron Davenport

Stat to know: The Jaguars -- who are in the midst of a 19-game losing streak (tied for second-longest in NFL history) -- have allowed 20-plus points in 22 straight games, the NFL's fourth-longest all-time streak.

Injuries: Titans | Jaguars

What to know for fantasy: Henry has 11 rushing scores in 10 career games against Jacksonville, including four in Week 14 of 2018 on his way to a career-high 47.8 points. See Week 5 rankings.

Betting nugget: Jacksonville has failed to cover in each of its last four games as a home underdog. Read more.

Davenport's pick: Titans 27, Jaguars 20
DiRocco's pick: Titans 21, Jaguars 17
FPI prediction: TEN, 61.4% (by an average of 4.0 points)

Matchup must-reads: Titans' struggles on third down costly against Jets ... Meyer apologizes again, says he didn't consider resigning as Jaguars coach

Browns (3-1) at Chargers (3-1)

4:05 p.m. ET | CBS
Matchup rating:
71.1 | Spread: LAC -2 (47)

What to watch for: The Browns' pass rush has been nearly unstoppable over the past two weeks with 11.0 sacks combined. Myles Garrett leads the NFL with six sacks. But Garrett and the Browns face a tough Chargers front, led by center Corey Linsley and rookie tackle Rashawn Slater. Los Angeles quarterback Justin Herbert has been pressured on just 25.6% of his dropbacks this season, fifth-lowest in the NFL, so the question becomes whether this front can keep Garrett and Co. away from Herbert. -- Shelley Smith

Bold prediction: The two defenses in this game will combine for eight sacks. The Chargers' Joey Bosa and the Browns' Garrett will lead the way with two apiece in a defensive struggle. The Browns rank No. 1 in the NFL in pass rush win rate, while the Chargers are No. 9. -- Jake Trotter

Stat to know: Chargers running back Austin Ekeler is averaging 5.7 yards per rush this season, the third-most in the NFL (min. 40 rushes). He has at least 100 scrimmage yards in three straight games, which is tied with Derrick Henry for the longest active streak in the NFL.

Injuries: Browns | Chargers

What to know for fantasy: Cleveland running back Kareem Hunt is widely viewed as the RB2 in Cleveland, but over the past two weeks, he's averaging more fantasy points (22.1) than Nick Chubb (19.9). See Week 5 rankings.

Betting nugget: Cleveland is 3-11 ATS against AFC opponents since the start of last season. Read more.

Trotter's pick: Chargers 20, Browns 18
Smith's pick: Chargers 24, Browns 14
FPI prediction: LAC, 54.8% (by an average of 1.7 points)

Matchup must-reads: Mayfield playing with partially torn labrum ... Veteran Cook establishing himself as key target for Herbert, Chargers ... After underwhelming showing vs. Vikings, Browns need a Baker bounceback ... Chargers' Murray possessing a heavy heart in aftermath of brother's death

Bears (2-2) at Raiders (3-1)

4:05 p.m. ET | CBS
Matchup rating:
35.9 | Spread: LV -5.5 (44)

What to watch for: The Khalil Mack "homecoming" has arrived. Talk about awkward. Mack never played for Las Vegas coach Jon Gruden, forcing a trade with his 2018 holdout, and called Oakland home for four years, never playing in Vegas. The last time the Raiders faced Mack was in London in 2019, and they held him sack-less. Mack and Raiders QB Derek Carr are close friends, and they always argued over who is faster. But with his battered offensive line, Carr might not want to find out on Sunday. -- Paul Gutierrez

Bold prediction: The Raiders will sack Bears quarterback Justin Fields five times. Fields -- Chicago's newly anointed permanent starting quarterback -- is incredibly mobile, but the Bears are without top running back David Montgomery and are therefore susceptible to being one-dimensional on offense on Sunday. The Browns sacked Fields nine times just two weeks ago. The Bears' offensive line is known to badly struggle against elite pass-rushers, and the Raiders have several of those. -- Jeff Dickerson

Stat to know: Carr has averaged 12.4 yards per attempt on third down this season, the most in the NFL.

Injuries: Bears | Raiders

What to know for fantasy: Bears receiver Allen Robinson II has averaged 1,199 receiving yards per season over the past two years, but he's on pace for just over half of that this season (633) -- and that includes an extra game. See Week 5 rankings.

Betting nugget: Not only has the under cashed in each of Chicago's past three games, none of them have seen more than 38 points scored. But Las Vegas is 15-5 to the over since the start of last season, the highest over percentage in the NFL. Read more.

Dickerson's pick: Raiders 28, Bears 17
Gutierrez's pick: Raiders 27, Bears 23
FPI prediction: LV, 62.3% (by an average of 4.3 points)

Matchup must-reads: Nagy commits to Fields as starting QB ... Has Crosby finally filled Raiders' sack gap left by Mack? ... Why the Bears are sticking with Fields at quarterback ... Raiders' tendency to start slow finally too much to overcome

49ers (2-2) at Cardinals (4-0)

4:25 p.m. ET | FOX
Matchup rating:
68.7 | Spread: ARI -5 (49.5)

What to watch for: This much we know about Sunday: The Cardinals will face either Jimmy Garoppolo or Trey Lance -- or both. Each presents their own unique game plan. Garoppolo is a pocket passer, while Lance is more of a dual-threat option, the likes of which the Cardinals' first-team defense sees every day in practice against their own Kyler Murray. If he starts, Lance would be the fourth-youngest quarterback to start his first game in the Super Bowl era, at 21 years and 154 days old. -- Josh Weinfuss

Bold prediction: Cardinals receiver DeAndre Hopkins will finish with 14-plus catches. The 49ers are still thin at cornerback, even as they hope to welcome back veteran Josh Norman, and Hopkins had 22 receptions in two games against San Francisco last season. Now the Niners have to account for the likes of A.J. Green and Rondale Moore, as well. This game could be tighter than many expect, but Hopkins could be the difference-maker. -- Nick Wagoner

Stat to know: The Cardinals can become the sixth team in NFL history with 30 points in each of the first five games of the season. A lot of that has to do with quarterback Kyler Murray's hot start. Only 5.5% of his passes from the pocket have been off-target incompletions. That's just 6 balls on 113 total attempts. And he is threading the needle downfield. According to ESPN route analysis powered by NFL Next Gen Stats, Murray has completed 17 of 24 passes when targeting vertical routes this year, the highest rate in the league.

Injuries: 49ers | Cardinals

What to know for fantasy: Last season, 49ers running backs racked up 98 fantasy points across their two games with the Cardinals. See Week 5 rankings.

Betting nugget: San Francisco is 8-2 ATS as a road underdog since the start of the 2019 season, while Arizona is 2-6 ATS as a home favorite under coach Kliff Kingsbury. Read more.

Wagoner's pick: Cardinals 30, 49ers 27
Weinfuss' pick: Cardinals 41, 49ers 24
FPI prediction: ARI, 62.8% (by an average of 4.6 points)

Matchup must-reads: How the NFL's leading receiver, the 49ers' Samuel, became more than a gadget guy ... Murray skews more pass, less run on way to 4-0 ... Cardinals' offense found a second dimension with 216 rushing yards against Rams

Giants (1-3) at Cowboys (3-1)

4:25 p.m. ET | FOX
Matchup rating:
52.6 | Spread: DAL -7 (52)

What to watch for: For as improved as the Cowboys have been defensively, big plays are still an issue. They have given up 21 plays of 20 yards or more through four games. The Giants have 16 plays of at least 20 yards and have a fully-loaded offense. Dallas has allowed five first downs this season on 3rd-and-10 or longer, so it will have to be mindful of New York QB Daniel Jones' ability to run and get the ball to receivers Kenny Golloday, Kadarius Toney and John Ross III, along with running back Saquon Barkley. -- Todd Archer

Bold prediction: Cowboys running back Ezekiel Elliott will rush for 150-plus yards. Elliott rushed for 143 against a good Carolina defensive front last week, and now he gets to face a Giants defense that has struggled to stop the run this season. New York is 20th in the NFL in that area, allowing 122.8 yards per game on the ground, and they haven't faced an offensive line like Dallas' unit. -- Jordan Raanan

Stat to know: Jones leads all NFL quarterbacks with a 71% completion percentage this season on passes that travel 15-plus yards downfield.

Injuries: Giants | Cowboys

What to know for fantasy: Cowboys QB Dak Prescott has a 75% completion percentage this season, second-best in the NFL. The Giants' defense has allowed the second-highest completion percentage, also at 75%. See Week 5 rankings.

Betting nugget: The Cowboys have won seven of their past eight games against the Giants, covering six of those contests. They are also the only team still unbeaten against the spread this season. Read more.

Raanan's pick: Cowboys 28, Giants 24
Archer's pick: Cowboys 37, Giants 33
FPI prediction: DAL, 72.9% (by an average of 8.4 points)

Matchup must-reads: Giants' Barkley showing signs he's back to top form ... What Prescott's gruesome injury was like for the Cowboys, Giants who were there: 'It just was surreal' ... Giants heap praise on QB Jones after first win of season ... Cowboys' Elliott-Pollard duo thriving during three-game win streak ... Cowboys' decision to cut Smith is about not stopping progress

Bills (3-1) at Chiefs (2-2)

8:20 p.m. ET | NBC
Matchup rating:
94.5 | Spread: KC -2.5 (56.5)

What to watch for: The Chiefs defended well against Buffalo QB Josh Allen and the Bills' offense in each of two games last season, but this is a different Kansas City defense, one with considerable weaknesses in many areas. The Bills are going to score some points. Can the Chiefs can outscore them? Kansas City scored a TD on every possession except one in last week's win over the Eagles, but Buffalo has the NFL's No. 1 scoring defense, so the task gets much more difficult this week. -- Adam Teicher

Bold prediction: The Bills will score at least 35 points against the Chiefs. They have scored at least that many in each of the last three games, and that trend should continue in Kansas City. The Chiefs' defense ranks 31st in points per game allowed (31.3) and has struggled to limit opposing offenses. While Allen's start to the season has been inconsistent, he'll take advantage of the opportunity in primetime. -- Alaina Getzenberg

Stat to know: Chiefs QB Patrick Mahomes can become the third player in the NFL history with at least three touchdown passes in each of his first five games of a season (Steve Young in 1998 and Tom Brady in 2007).

Injuries: Bills | Chiefs

What to know for fantasy: Bills running back Zack Moss' carry count has increased each week this season, and he has found paydirt four times in those three games (did not play in Week 1). See Week 5 rankings.

Betting nugget: Kansas City is 0-3 ATS against teams with winning records this season. Read more.

Getzenberg's pick: Bills 37, Chiefs 30
Teicher's pick: Bills 38, Chiefs 34
FPI prediction: BUF, 50.6% (by an average of 0.3 points)

Matchup must-reads: Knox emerging as receiving TE threat Bills desperately needed ... From high school to college, games that shaped the mentality of Mahomes

Colts (1-3) at Ravens (3-1)

Monday, 8:15 p.m. ET | ESPN
Matchup rating:
59.4 | Spread: BAL -7 (46)

What to watch for: All eyes will be on Colts quarterback Carson Wentz against the Ravens' pass rush. The last time Wentz played Baltimore, he was sacked six times (tied for the second-most in his career). The Ravens are coming off a game in which they recorded five sacks in Denver, and Indianapolis will again be without three-time All-Pro guard Quenton Nelson (sprained right ankle). -- Jamison Hensley

Bold prediction: Baltimore quarterback Lamar Jackson will pass for more than 300 yards. The Colts, like many teams, are focused on slowing down Baltimore's running game that has topped 100 yards on the ground in 43 straight games. Jackson had his first 300-yard passing game of the season (316) in Week 4 at Denver, and Colts coach Frank Reich said Jackson's passing ability is an "underrated" part of his game. -- Mike Wells

Stat to know: After leading the league in first-down designed rush percentage over 2018-20, the Ravens are just 11th this season.

Injuries: Colts | Ravens

What to know for fantasy: Since the beginning of 2019, the Ravens have won six primetime games. In those contests, Jackson is averaging 34 fantasy points, 94.5 rushing yards and more than a rushing score per game. See Week 5 rankings.

Betting nugget: Home teams are 4-0 ATS on Monday Night Football this season. Read more.

Wells' pick: Ravens 30, Colts 20
Hensley's pick: Ravens 30, Colts 10
FPI prediction: BAL, 67.2% (by an average of 6.1 points)

Matchup must-reads: How Colts quarterback Wentz took a step in right direction ... Just crazy:' Ravens want everyone to stop thinking Jackson can't throw ... Ravens to submit unpenalized hits on QB Jackson to NFL