The Week 6 NFL schedule for the 2021 season is stacked with great matchups, and we've 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 6 slate, including a big showdown between Lamar Jackson and Justin Herbert, another trip to London and a chess match between the Cowboys and Patriots. It all culminates with a Monday Night Football matchup between the Bills and the Titans on ESPN. (Game times are Sunday unless otherwise noted.)
9:30 a.m. ET | CBS | London
Matchup rating: 13.6 | Spread: MIA -3 (47)
What to watch for: Dolphins QB Tua Tagovailoa is expected to return -- and under must-win stakes. If the Dolphins don't win at least two of their next three games, they'll be left with a record only one other team in modern NFL history has ever come back from to make the playoffs. So the pressure is on the second-year quarterback to resuscitate a stagnant offense (31st in yards per game and 30th in passing yards per game) in London. -- Marcel Louis-Jacques
Bold prediction: Jaguars QB Trevor Lawrence and Tagovailoa will each throw for more than 300 yards. Both teams' pass defenses rank in the bottom quarter of the league. They have allowed a combined 19 touchdown passes, have intercepted just three passes and are each giving up more than 280 passing yards per game. -- Mike DiRocco
Stat to know: The Jaguars have not made a field goal this season. They are the first team since the 1962 Vikings to go without a field goal five games into a season, and the last team without a made field goal through six games was the 1956 Baltimore Colts.
What to know for fantasy: Jacksonville running back James Robinson averages 19.2 fantasy points and 4.9 yards per carry for his career when getting at least 15 carries in a game, and he has at least 15 carries in three straight contests. See Week 6 rankings.
Betting nugget: Favorites are 18-11 against the spread (ATS) in London games. But Miami has the worst cover margin in the NFL this season (minus-11.2) and lost outright the only other time it was favored this season. Read more.
DiRocco's pick: Jaguars 28, Dolphins 24
Louis-Jacques' pick: Dolphins 21, Jaguars 14
FPI prediction: MIA, 61.9% (by an average of 4.2 points)
Matchup must-reads: Jaguars RB Robinson needs an even heavier workload -- especially in critical situations ... Tagovailoa practices in step toward return from IR ... Flores 'concerned about defense' after drubbing
1 p.m. ET | CBS
Matchup rating: 72.2 | Spread: BAL -2.5 (52)
What to watch for: All eyes will be on the quarterbacks: the Chargers' Justin Herbert vs. the Ravens' Lamar Jackson. This is a clash of two of the NFL's best young quarterbacks who are at the top of their games right now. It's only the second matchup in league history in which both quarterbacks are coming off games of 400 total yards and four touchdown passes the prior week. Over the past three games, Herbert leads the NFL with 11 touchdown passes, while Jackson ranks second in the league with 1,045 yards passing. -- Jamison Hensley
Bold prediction: Herbert will throw for at least 400 yards, and Chargers running back Austin Ekeler will rush for at least 250. It's going to be that big of a day on offense. Herbert's poise and patience will be key against the Ravens' defense as he tries to keep a five-game streak of at least 25 completions alive. -- Shelley Smith
Stat to know: The Chargers are allowing an NFL-high 157.6 rushing yards per game and 5.6 yards per rush this season. The Ravens, meanwhile, rank fourth in rushing yards per game (148.8) and sixth in yards per rush (4.9).
What to know for fantasy: Ekeler is just the fifth player over the past 35 years to record 55 rushing yards and a receiving touchdown in three straight games, and his seven total touchdowns are tied for the NFL lead through five weeks. See Week 6 rankings.
Betting nugget: The over has hit in each of the past six games in which the Ravens had less than full rest, something that will be the case this week after Baltimore hosted Indianapolis on Monday night. Read more.
Smith's pick: Chargers 24, Ravens 21
Hensley's pick: Chargers 37, Ravens 34
FPI prediction: BAL, 58.7% (by an average of 3.1 points)
Matchup must-reads: Williams' chemistry with Herbert helping Chargers reach new heights ... Ravens believe unreal finishes are the start of something special ... Four wild NFL Week 5 finishes and lessons from wins by the Chargers, Packers, Vikings and Eagles ... Ravens QB Jackson gives ref shoutout for Monday night roughing call
1 p.m. ET | CBS
Matchup rating: 57.5 | Spread: KC -6.5 (54.5)
What to watch for: Will Washington's defense be able to contain Chiefs quarterback Patrick Mahomes? Washington ranks 27th in passing yards allowed per game, 22nd in yards per pass attempt allowed and tied for 31st in touchdowns allowed of 20 yards or more. The secondary has not been consistent, to say the least, and a coverage is blown each game. It would help if Washington's ground game takes over against a defense ranked 29th vs. the run -- it could lead to points and limit the Chiefs' time with the ball. -- John Keim
Bold prediction: Chiefs receiver Tyreek Hill will go over 100 yards and catch a couple of TD passes. It has been an unusual season for Hill, who has two big games with almost 200 yards and three games in which he wasn't much of a factor. But he'll bounce back after last week's poor showing against the Bills with a big game against Washington, which is allowing a generous opponent passer rating of 107.8. -- Adam Teicher
Stat to know: The Chiefs are allowing nearly 7.08 yards per play, which is the second-worst rate through five games in NFL history (1950 Baltimore Colts at 7.11), according to Elias Sports Bureau research.
Betting nugget: The Chiefs were 7-3 ATS as a road favorite of 3-plus points in the first two years of the Mahomes era. Since then, they are just 3-5 ATS in such spots. Read more.
Teicher's pick: Chiefs 37, Washington 31
Keim's pick: Chiefs 35, Washington 29
FPI prediction: KC, 65.5% (by an average of 5.5 points)
Matchup must-reads: Mahomes won't point to Chiefs' defense to explain his turnover troubles ... Rivera frustrated as missed opportunities mount ... MCL sprain to sideline Edwards-Helaire 'a few weeks' ... Chiefs address weekly burden of being in the 'crosshairs'
1 p.m. ET | Fox
Matchup rating: 56.8 | Spread: MIN -1 (46)
What to watch for: Keep an eye on Carolina's offensive line. It has given up eight sacks and 19 quarterback hits the past two weeks, a big reason for a two-game losing streak. The Vikings rank second in the NFL in sacks with 17, so they can get after the QB. The Panthers likely will have back the left side of their line (tackle Cameron Erving and guard Pat Elflein), but even with them, teams were getting pressure on Sam Darnold. -- David Newton
Bold prediction: Darnold will notch his seventh career game with three interceptions, which will be the most by any quarterback since he entered the NFL in 2018. The Vikings' pass rush ranks second with 3.4 sacks per game, and we saw how Darnold reverted back to his Jets form (i.e., holding on to the ball too long, making poor decisions) in Week 5 when he took blow after blow while facing pressure on 43% of his dropbacks. What Minnesota does up front will yield a big day on the back end of the defense in the form of multiple interceptions by the secondary. -- Courtney Cronin
Stat to know: The Panthers' defense is allowing 4.75 yards per play -- only the Bills (4.25) are allowing fewer -- and is leading the NFL in pass rush win rate.
What to know for fantasy: Minnesota quarterback Kirk Cousins is averaging 26.3 fantasy points per game over his past four on the road, averaging over 320 passing yards in the process with 11 scores and 0 interceptions. See Week 6 rankings.
Betting nugget: Carolina is 4-1 ATS in its past five games when the line is between +3 and -3. Minnesota is 1-4 ATS in its past five in that spot. Read more.
Cronin's pick: Vikings 24, Panthers 21
Newton's pick: Panthers 27, Vikings 24
FPI prediction: CAR, 54.3% (by an average of 1.5 points)
Matchup must-reads: Unimpressive win over Lions highlights flaws with Vikings' conservative approach ... Can Panthers' Darnold, Anderson re-create chemistry found with Jets ... Darnold knows he has to perform better under pressure
1 p.m. ET | Fox
Matchup rating: 51.3 | Spread: LAR -9.5 (48)
What to watch for: The Rams have allowed a league-low four sacks through five games, and only one team has produced fewer than the Giants' eight sacks. Can New York get near Rams quarterback Matthew Stafford? If not, it's going to be another long day for the Giants' defense and a good afternoon for Stafford and Los Angeles. -- Jordan Raanan
Bold prediction: Stafford will pass for four touchdowns in a blowout win. The Giants' defense is allowing 27.8 points per game, which ranks 27th in the NFL, and it has given up 10 passing touchdowns, which ranks 21st. Stafford's connection has been just a bit off with receivers the past two games, so look for coach Sean McVay to dial up the passing game to get him in rhythm with his playmakers early. -- Lindsey Thiry
Stat to know: The Rams lead the NFL this season in offensive efficiency (82.0) and yards per play (6.71).
What to know for fantasy: Los Angeles running back Darrell Henderson has accounted for 72.9% of the Rams' RB touches in his four games this season. That's a higher rate than Dalvin Cook and Austin Ekeler hold this season with their respective teams. See Week 6 rankings.
Betting nugget: Over the past five seasons, New York is 9-24-1 ATS at home and 7-18 ATS as a home underdog. Read more.
Thiry's pick: Rams 35, Giants 21
Raanan's pick: Rams 28, Giants 17
FPI prediction: LAR, 69.1% (by an average of 6.9 points)
Matchup must-reads: 'Just sad about it': Rams' McVay speaks on resignation of mentor Gruden ... Jones 'on track' to return from concussion protocol, face Rams ... Stafford says thumb is fine, Woods gets going in Rams' offense ... Toney is the new 'Human Joystick' and a fun addition to Giants offense
1 p.m. ET | Fox
Matchup rating: 49.5 | Spread: GB -5 (44.5)
What to watch for: Believe it or not, the Bears are within one game of the Packers in the NFC North. A victory over hated Green Bay would do wonders for Chicago's confidence. The Packers, meanwhile, are just hoping for business as usual. Green Bay quarterback Aaron Rodgers (20-4 lifetime versus Chicago) has trounced the Bears throughout his illustrious career. -- Jeff Dickerson
Bold prediction: Rodgers' turnover-free streak during the Packers' current four-game winning streak against the Bears will come to an end -- and it will cost them the game. Rodgers has 10 touchdown passes without a turnover in the past four meetings with Chicago, but the Bears' defense looks strong this season and could be the difference in pulling off an upset. -- Rob Demovsky
Stat to know: Justin Fields will be the 20th different starting quarterback that the Bears have used against the Packers since 1992. The Packers have used only three different starting QBs vs. the Bears during that span.
What to know for fantasy: Pass-happy game script? Packers receiver Davante Adams has scored or gone over 115 receiving yards in seven of his past eight games against the Bears, while running back Aaron Jones averages under 4.0 yards per carry for his career against Chicago, never totaling more than 90 total yards in a game in the process. See Week 6 rankings.
Betting nugget: The Packers have won nine of the past 10 meetings in this rivalry, covering the spread in seven of those instances. Read more.
Demovsky's pick: Bears 21, Packers 20
Dickerson's pick: Packers 25, Bears 23
FPI prediction: GB, 59.1% (by an average of 3.2 points)
Matchup must-reads: Rodgers runs out of time when trying to recall all of the Bears' QBs since 2008 ... Bears' Fields says he'll be OK to play vs. Packers ... How LB Campbell went from out of work to star of Packers' defense ... Bears showing offensive identity under new playcaller Lazor
1 p.m. ET | CBS
Matchup rating: 29.7 | Spread: IND -10 (43.5)
What to watch for: Will the Colts' pass rush have a big game against Houston's depleted offensive line? The Texans will be without their best offensive lineman, left tackle Laremy Tunsil (finger), against the Colts. That means an Indianapolis front led by DeForest Buckner will have an opportunity to put pressure on Houston rookie quarterback Davis Mills, who has been sacked 11 times in four games. And there's a chance the Colts could have rookie pass-rusher Kwity Paye (hamstring) back after he missed the past two games. -- Mike Wells
Bold prediction: If Colts receiver T.Y. Hilton returns from injury (neck) and plays on Sunday, he'll continue his success against the Texans with a big game, reaching 100 receiving yards. In 18 career games against Houston, Hilton has 97 catches for 1,718 yards and 11 touchdowns. -- Sarah Barshop
Stat to know: After throwing for 312 yards last week, Mills can become the first Texans rookie with 300-plus passing yards in consecutive weeks.
What to know for fantasy: In each of the past five seasons, Hilton has had a game with over 19 fantasy points against Houston as Indianapolis' WR1. Michael Pittman Jr. has that role these days, and the Houston defense isn't exactly intimidating. See Week 6 rankings.
Betting nugget: Indianapolis is 12-4-1 ATS against Houston since 2013. Read more.
Barshop's pick: Texans 24, Colts 21
Wells' pick: Colts 27, Texans 13
FPI prediction: IND, 72.3% (by an average of 8.1 points)
1 p.m. ET | Fox
Matchup rating: 23.5 | Spread: CIN -3.5 (47)
What to watch for: Although the Lions are one of two winless teams, this group could easily have two wins this year if it weren't for gut-wrenching losses to Baltimore and Minnesota on game-deciding field goals. So can they avoid starting 0-6 for the first time since 2008, when the squad infamously finished 0-16? (First-year Lions coach Dan Campbell actually experienced that as a player.) "I know, I know. And look, nothing I'm going to tell them is going to make them feel any better," Campbell said to any disappointed fans. "All I can do is try to prove it, show it -- not me, us, all of us, staff, players. Look, everybody is frustrated." -- Eric Woodyard
Bold prediction: Bengals wide receiver Ja'Marr Chase will have a 40-yard completion and 125 receiving yards. The Lions give up more yards per completion than any other team. With the Bengals' rushing attack a question mark because of injuries and COVID-19, Cincinnati could do some serious damage in the air. And so far, Chase has been the team's big-play receiver. -- Ben Baby
Stat to know: Joe Burrow is the first QB in Bengals history with multiple touchdown passes in each of the team's first five games. He seeks to join Dan Marino (1984) as the only first- or second-year quarterbacks with multiple passing touchdowns in their teams' first six games.
What to know for fantasy: Chase is the second rookie WR with 450 receiving yards and five receiving TDs through five games. The other? Randy Moss in 1998. See Week 6 rankings.
Betting nugget: Cincinnati is 1-4 ATS as a favorite under coach Zac Taylor (since 2019). Read more.
Baby's pick: Bengals 27, Lions 23
Woodyard's pick: Lions 24, Bengals 21
FPI prediction: CIN, 56.1% (by an average of 2.2 points)
4:05 p.m. ET | Fox
Matchup rating: 77.4 | Spread: CLE -3 (49.5)
What to watch for: After giving up 47 points to the Chargers last weekend, how will the Browns' defense respond against Cardinals QB Kyler Murray and his array of talented skill players? It won't be easy to bounce back, especially with defensive ends Myles Garrett and Jadeveon Clowney and cornerback Denzel Ward limited in practice this week due to injuries. -- Jake Trotter
Bold prediction: The Cardinals will hold the Browns' top-ranked rushing attack to under 100 yards in one of Arizona's best defensive efforts of the season. The Browns are averaging 187.6 yards per game on the ground, and the Cardinals are giving up 139 -- but the Cardinals have proved they can stop big-time rushing attacks. Just look at what they did in Week 1 to Tennessee's Derrick Henry, when they held him 58 yards and the Titans to 86. -- Josh Weinfuss
Stat to know: Arizona receiver DeAndre Hopkins now has seven straight games without 100 yards receiving, his longest streak since 2016. He had a season-high 87 receiving yards last week.
Betting nugget: The Browns are 12-1 outright in their past 13 home games when not facing the Ravens. Read more.
Weinfuss' pick: Cardinals 31, Browns 28.
Trotter's pick: Cardinals 34, Browns 33
FPI prediction: CLE, 51.9% (by an average of 0.7 points)
Matchup must-reads: Kingsbury finally has the players to run his offense ... How Mayfield and Murray pushed each other to greatness at Oklahoma ... Jones tests positive for COVID-19 ... Defense has been the difference for unbeaten Cardinals
4:25 p.m. ET | CBS
Matchup rating: 67.6 | Spread: DAL -3.5 (50.5)
What to watch for: Cowboys cornerback Trevon Diggs knows Patriots QB Mac Jones well from their time together as teammates at Alabama. Diggs, a second-round pick in 2020, became only the second Cowboys defender to record an interception in each of the first five games of a season (Don Bishop, 1961). Jones, the Patriots' 2021 first-round pick, used to face Diggs in practice as Alabama's scout-team QB and already knows what it's like to be picked by him. "He has a really good feel for the game," Jones said. -- Mike Reiss
Bold prediction: The Patriots will score more than 21 points. That might not sound bold, but they have scored more than 21 points in just three of their past 11 home games -- and haven't reached the mark in any of their three home games this year. As improved as the Cowboys' defense is, it still gives up too many big plays, allowing 25 plays of 20 yards or more in five games. Dallas has lived on takeaways and offensive proficiency. The Patriots will have some chances, and Jones will put some points on the board. -- Todd Archer
Stat to know: The Cowboys rank fifth in offensive efficiency and seventh in defensive efficiency this season. They are the only team in the league to rank in the top seven in both.
Betting nugget: Dallas is the only team in the NFL that is still undefeated against the spread this season (5-0 ATS). It's the first team to start 5-0 ATS since 2018 Kansas City (7-0 ATS). Read more.
Archer's pick: Patriots 28, Cowboys 26
Reiss' pick: Patriots 27, Cowboys 24
FPI prediction: DAL, 56.0% (by an average of 2.1 points)
Matchup must-reads: How Cowboys cornerback Diggs' game, name are growing quickly ... Jones' poise stands out in leading winning drive ... Cowboys' offense puts up 515 yards, shows it's always 'in the strike zone' ... Judon to wear pink in honor of mother's breast cancer battle
4:25 p.m. ET | CBS
Matchup rating: 47.9 | Spread: DEN -3.5 (44.5)
What to watch for: What will the Broncos' defense do against a Raiders offense in turmoil, and specifically quarterback Derek Carr? In Carr's past three trips to Denver, he has thrown for 288, 391 and 371 yards with four touchdowns across those three games. The Broncos' pass rush has been lukewarm over the past two games, and the group needs a big day in this one if the Broncos want to get a win they need. -- Jeff Legwold
Bold prediction: Trying to compartmentalize the emotional roller coaster the Raiders have ridden this week is tough. So, too, will be keeping Denver edge rusher Von Miller in check, or have you missed Las Vegas' reimagined offensive line being unable to keep Carr clean? Carr is on pace to be sacked a career high-tying 51 times, and Miller -- who has 4.5 sacks this season -- will break through with at least two more against the Raiders. -- Paul Gutierrez
Stat to know: Raiders running back Josh Jacobs is averaging 3.2 yards per rush this season, the third-lowest mark in the NFL among qualified running backs and ahead of only Mark Ingram II and James Conner.
What to know for fantasy: Broncos running backs have had next to no success recently against the Raiders. Over the past five meetings, they've scored just once on 107 carries. And in the past three matchups, they've managed just 3.4 yards per carry. See Week 6 rankings.
Betting nugget: Under tickets have cashed eight times in the past nine games between the Broncos and Raiders. Read more.
Gutierrez's pick: Broncos 20, Raiders 10
Legwold's pick: Broncos 23, Raiders 17
FPI prediction: DEN, 62.8% (by an average of 4.5 points)
Matchup must-reads: Gruden built a bad Raiders roster: Why his tenure was a disaster ... Physics professor explains why Broncos' Williams is hard to bring down ... Where do the Raiders go after Gruden's abrupt departure? ... Slow starts a growing problem for Broncos
8:20 p.m. ET | NBC
Matchup rating: 42.1 | Spread: PIT -5 (42.5)
What to watch for: No, the Steelers aren't facing Russell Wilson, but that doesn't mean they're taking the Seahawks' Geno Smith lightly. Pittsburgh coach Mike Tomlin stressed that Seattle can still run the same offense with him. The Steelers' defense looked better a week ago against the Broncos, in part because the offense sustained drives, but they have to replicate that again this week and make Smith uncomfortable by generating a stronger pass rush than they've managed in recent weeks. -- Brooke Pryor
Bold prediction: Seattle's Gerald Everett and Will Dissly will combine for 100 receiving yards and a touchdown. Tight ends haven't factored into Seattle's passing game under new coordinator Shane Waldron as much as many expected, and that was the case even before Everett missed two games while on COVID-19/reserve. That could change with Smith replacing an injured Wilson. The prediction here is that Smith won't push the ball down the field as much as Wilson, opening up opportunities for Everett and Dissly on underneath routes. -- Brady Henderson
Stat to know: The Seahawks have allowed 450 yards of offense in four straight games, which is tied for the longest streak in NFL history.
What to know for fantasy: Over the past decade, four of the top nine prime-time fantasy performances from a running back have come from a rookie (Alfred Morris in 2012, David Johnson in 2015 and Kareem Hunt twice in 2017). Steelers running back Najee Harris has rushing touchdowns in consecutive games. See Week 6 rankings.
Betting nugget: Smith is 5-0 ATS in his past five starts (his final four with the Jets and his only start with the Giants). Read more.
Henderson's pick: Steelers 23, Seahawks 21
Pryor's pick: Steelers 24, Seahawks 20
FPI prediction: PIT, 59.3% (by an average of 3.3 points)
Matchup must-reads: Seahawks need more from Adams to turn struggling defense around ... Tomlin says it will take collective effort for Steelers to fill void left by Smith-Schuster's injury ... With Wilson out due to injury, what's next for Seahawks, Smith?
What to watch for: Something has to give. The Bills' defense is giving up 78.4 rushing yards per game, third best in the NFL. Tennessee's Derrick Henry is leading the league with 640 rushing yards and has four consecutive games with at least 100 yards on the ground. Henry had only 57 rushing yards in the Titans' 42-16 win over the Bills last season. -- Turron Davenport
Bold prediction: The Bills will limit Henry to his second game this year under 100 rushing yards and give the Titans' offense some issues. This season under defensive coordinator Leslie Frazier, the Bills have adapted to defending whatever offense is thrown at them. So while the Titans are averaging 167.8 rush yards per game this season (third most in the NFL), only three teams are giving up fewer yards per rush than the Bills' 3.7. -- Alaina Getzenberg
Stat to know: The Bills have scored 35-plus points in four straight games -- tied for the longest streak in franchise history. They could become the first team to score 35-plus points in five straight games since the Broncos in 2012-13.
What to know for fantasy: Tennessee QB Ryan Tannehill's top four games as a member of the Titans have come at home, including a 30-point effort against these Bills in Week 5 of last season. See Week 6 rankings.
Betting nugget: Buffalo has the best cover margin in the NFL (plus-15.3). That's the fourth-best mark by any team through five games in the past 20 seasons. Buffalo has covered four straight games, all by at least 15 points. Read more.
Getzenberg's pick: Bills 35, Titans 24
Davenport's pick: Bills 35, Titans 31
FPI prediction: BUF, 72.4% (by an average of 8.2 points)
Matchup must-reads: After Allen leads statement win over Chiefs, what's next for Bills? ... Titans OC Downing employed creative playcalling against Jaguars ... Allen teams with fans to sell retro high school sweatshirts