NFL Week 6 betting odds, picks, tips: Who to take in Chiefs-Bills and more

Week 6 of the 2022 NFL season is the first of the year with teams on byes (Detroit, Tennessee, Las Vegas, Houston), but there are still plenty games to keep an eye on, including the Sunday night matchup between the Dallas Cowboys and Philadelphia Eagles.

But what does this all mean from a betting perspective? And what are the best plays to help you make smart wagering decisions?

Betting analysts Doug Kezirian, Tyler Fulghum, Joe Fortenbaugh, Anita Marks and Erin Dolan, fantasy and sports betting analysts Eric Moody and Andre Snellings, ESPN Stats & Information's Seth Walder and Football Outsiders' Aaron Schatz offer their insight into the games with tips and picks.

Note: Lines from Caesars Sportsbook unless otherwise indicated.

What is your biggest betting storyline entering Week 6?

Doug Kezirian: On a macro level, I would say it's how many backup quarterbacks we have seen and how we handicap those games. Some, such as Cooper Rush, have shined. Others have looked very bad. Oddsmakers and the betting market are kind of lost with how to assess power ratings with these backup quarterbacks.

Joe Fortenbaugh: Teams traveling back from London. There have been seven instances in which a team played in London and then immediately in America the next week without going on a bye. In those seven instances, the opponent of the London team has gone over their team total six times. We saw it happen twice last week with the Bears eclipsing their team total against the Vikings and the Seahawks eclipsing their team total against the Saints (Minnesota and New Orleans had played in London the week prior). As a result, I like the Jets to go over 18.5 points against the Packers and the Ravens to go over 25.5 points against the Giants, as Green Bay and New York faced each other last week across the pond.

Aaron Schatz: The biggest game of the week is Buffalo and Kansas City, and that's the biggest betting storyline as well because Patrick Mahomes is a home underdog for the first time in his career. The Chiefs are 7-0-1 against the spread when they've been underdogs with Mahomes at quarterback. Can the Bills break that streak and, more importantly, win this game?

Anita Marks: I agree with Aaron ... the biggest gambling story is Buffalo and K.C. I'm just as intrigued with Lamar Jackson and the Ravens traveling to New Jersey for an appointment with Wink Martindale and the N.Y. Giants. Wink was the Ravens' DC for four seasons -- facing Lamar Jackson at practice and probably knows his tendencies better than any other DC in the league. However, Wink plays a ton of man and blitzes at a 43% rate. Lamar has the fourth-best QB rating in the league against blitz/man coverage (136.5). We will be watching the ultimate game of Battleship! I'll take Captain Lamar and the Ravens team total over 25.5 points (-115).

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The Kansas Chiefs (+3) are home underdogs for the first time in Patrick Mahomes' career in a rematch of the AFC Championship game against Josh Allen and the Buffalo Bills. What are your thoughts on the side and total (54) for this game?

Kezirian: This has all the makings of a shootout, and I believe 54 is too low. It's pretty simple. These two teams rank first and second in offensive efficiency, and the Chiefs' defense is among the league's worst. Plus, each quarterback is his team's best player and will have the green light to sling it. Give me the over.

Fortenbaugh: I'm playing Buffalo over 28.5 points (-105). Short week for a Kansas City defense that absolutely stinks defending the pass. And it's not like Buffalo is scared to play at Arrowhead Stadium. The Bills went 1-1 at Kansas City last year while scoring 36 or more points both times. I'm expecting a big game from Stefon Diggs.

Schatz: I'm staying away from the spread, which I think is right on the money given how good these teams have been this season. Instead, I'll go with an under-54 play because I think these defenses are a bit underrated. Buffalo is currently No. 2 in defensive DVOA. The Bills' defense has been better than their offense this year! The Chiefs aren't as good on that side of the ball, but they're an average defense this season, which is more than we usually expect from them. I know how good these quarterbacks are, but 54 is a high number to hit.

Erin Dolan: Hard not to back the over here. Including playoffs, the average total for Josh Allen vs. Mahomes in their four matchups is 55 points, and each of their past three meetings have hit the over. That average total for these QBs is the highest for any QB matchup in the last 35 seasons. Also of note, completely agree with Joe Fortenbaugh's analysis above. Kansas City's defense is not that good and Allen and company should feast on that.

Eric Moody: Bettors are expecting a high-scoring game between the Bills and Chiefs. That's what I think too. Allen and Mahomes have played at MVP levels this season. The last three matchups between Buffalo and Kansas City have averaged 66 total points, with each outing surpassing this week's total. In terms of points per game this season, the Chiefs are first with 31.8 and the Bills are second with 30.4. While Buffalo will want revenge for their demise the last two seasons, I'm taking Kansas City and the points. At home, the Bills offense averages 39.5 points per game, while on the road, it averages only 24.3 points per game. Regardless, I'm sure the AFC showdown will be exciting to watch and will have numerous twists and turns.

Andre Snellings: I'll take the Chiefs with the points and the over. These were expected to be two of the best teams in the league entering the season, and they've been exactly that so far. I expect this to be a competitive game and for both teams to put plenty of points on the board. In a game that I consider a pick 'em that could go down to the wire, I like having that field goal leeway in my team's favor. The two times these teams played last season, they combined for 58 points in regulation both times (64 points total in overtime, in the playoffs matchup). I'm expecting a similar outcome this time around.

Marks: How often are we going to get Reid and Mahomes as a home 'dog!?!? Sign me up! K.C.'s Chris Jones should make things uncomfortable for Allen behind the interior of his offensive line, which ranks 26th in the NFL. The Chiefs expect to get CB Trent McDuffie back, and the Bills are still dealing with a number of injuries in their secondary. The Bills play a lot of zone coverage, an area where Mahomes thrives. Ref Brad Allen will be officiating this matchup, where home underdogs cover 67% since 2016 under his watch.

The Dallas Cowboys head to Lincoln Financial Field to face the undefeated Philadelphia Eagles in a battle for NFC East supremacy. Philadelphia is currently a 6-point favorite and the total for the game is 42. Who are you taking and who do you like to win the division this year (Cowboys +340, Eagles -320)?

Fortenbaugh: Under 42 points. Philly is banged up along the offensive line and facing a solid Dallas defense that has yet to surrender more than 19 points in a game. On the other side of the field stands Cooper Rush and a Cowboys offense that ranks 24th in scoring. This is a good Philly defense that will have the benefit of a raucous Lincoln Financial Field at its back.

Schatz: I've been driving the Eagles bandwagon since they were my NFC Super Bowl pick in the preseason, and I'm not going to stop now that they're 5-0. The Eagles have a top-five offense and defense by DVOA. They're the better offense and an equal defense, and they're at home, so give me Eagles -6. I'm also taking the Eagles to win the division, in particular because they have the easiest remaining schedule in the league, but I wouldn't put money down with those odds because they almost exactly match what we have in our playoff odds simulation at Football Outsiders.

Dolan: Philly first half -3. It's an automatic play until the Eagles drop the ball on this. They are outsourcing opponents 106 to 45 in the first half this season -- by far the best such scoring margin in the NFL. The Eagles are also the fourth team in the past 15 seasons to not trail in the second half through their first five games. The Cowboys defense is no joke, but Dallas is averaging 11 points in the first half this season and Philly is leading the league averaging 21. Philly starts off fast.

Moody: I'm backing the Eagles to cover the spread. Averaging 419.8 total yards per game, Philadelphia's offense has been lethal this season. The Bills (440.4) are the only team that averages more. Although the Cowboys defense has been outstanding, they have faced the Buccaneers, Bengals, Giants, Commanders and Rams so far this season. In total yards per game, none of those offenses rank inside the top 15. They have also faced offensive lines that rank near the bottom of the league in pass block win rate. As I see it, the Eagles' offensive line is one of the best in the league, and that will make a huge difference in this matchup. I'd bet on the under in this matchup. The under is 10-1-1 in the Cowboys' past 12 games following a straight-up and against-the-spread win. Philadelphia is still the clear favorite to win the NFC East. By defeating the Cowboys, the Eagles could begin to separate themselves from the pack.

Snellings: I'll take the Cowboys with the points. In a battle of two elite defenses, getting a full touchdown plus half an extra point is a lot. The Cowboys have yet to learn how to lose with Rush at quarterback, and they play a clock-controlling, ground-heavy game that does just enough with their defense keeping it close. I'm not sure they have enough to get by the Eagles playing that way, but I do think they'll keep it competitive.

For the NFC East, I was in on the Eagles during the offseason when I could get them at underdog odds. But the Cowboys are too good for it to be a clear advantage for either team moving forward. So, right now, I'd take the Cowboys at +340 because I don't believe the Eagles are three times more likely than them to win the division.

Marks: Fly Eagles Fly ... and grab them at -6.5. Who have the Boys beaten? A Bengals team after Joe Burrow's appendix burst, the Giants, Washington and a horrible Rams team!? Rush is expected to be under center and, albeit a great storyline, he only has passed for six touchdowns in five games. That is not going to cut it against the high-flying Eagles. Dallas is barely getting into the red zone (30th in the NFL) and only 35% of their scoring is touchdowns. Ref John Hussey will be calling this game, and home teams have the best winning percentage under Hussey (67%, 73% in division games) since 2016.

What are the three most important things that our analytics say?

Walder: Here's three sides against the spread that FPI likes.

Buffalo Bills at Kansas City Chiefs (+2.5)
Sunday, 4:25 p.m. ET, GEHA Field at Arrowhead Stadium, Kansas City

FPI considers the Chiefs to be the best team in football, so it actually favors Kansas City by a field goal here. The Chiefs are the better offense; they average 0.05 expected points added per play more than the Bills, meaning they generate an extra three points over 60 plays from scrimmage. That's nothing. And while the Bills have been -- and are -- much, much better than the Chiefs, past defensive performance is less indicative of future performance than past offensive performance is for future offense. I expect our prediction will tighten if some questionable Bills players, like safety Jordan Poyer, are able to play -- but I imagine the model still will prefer the Bills.

New England Patriots at Cleveland Browns (-2.5)
Sunday, 1 p.m. ET, FirstEnergy Stadium, Cleveland

The Browns' offensive efficiency has been remarkable despite having Jacoby Brissett at quarterback. Cleveland ranks first in EPA per designed run play and ninth per dropback. That's really good! And their ground game is good enough that they can keep running the ball, and it's not actually costly the way it is for most teams. Now, Cleveland's defensive efficiency? Eek, that's another story. But again, defense is less predictable. So the fact that we believe Cleveland is a good offense is worth roughly twice as much as us believing the Browns have a poor defense.

Jacksonville Jaguars (+2.5) at Indianapolis Colts
Sunday, 1 p.m. ET, Lucas Oil Stadium, Indianapolis

From FPI's perspective, the Jags' ought to be field goal favorites here. Indianapolis' offense is miserable, ranking literally worst in the league in EPA per play. The Jaguars aren't perfect, but they rank 18th in the same category ... and that's their worse side of the ball. The Jaguars rank third in EPA per play on defense to the Colts' 11th. The Jags are just straight up the better team, and that more than makes up for home-field advantage. And in case you forgot, just a few weeks ago the Jaguars shut out this very same Colts team.

What is your best bet for Week 6?

Kezirian: Vikings -3. Statistically, the Dolphins offense really takes giant steps backward with Skylar Thompson at quarterback. I just don't see how they maintain pace with a Vikings offense that ranks sixth in offensive efficiency. Since this is not a prime time game, I am comfortable backing Kirk Cousins.

Fortenbaugh: Jets team total over 18.5 points. I think the Green Bay defense will be gassed traveling back from London, and this Jets offense, shockingly, ranks 11th in the NFL in scoring at 23.2 points per game.

Schatz: I'm happy to take Jacksonville +2.5 at Indianapolis this week. The Jaguars are currently seventh in the league in DVOA based on their play through five games. No, they aren't really that good, but our DAVE ratings which combine 2022 with preseason projections still put them 17th. Meanwhile, the Colts are dead last in DVOA right now despite a 2-2-1 record. They are easily the worst offense in the league and would be even worse if they lost more of those fumbles they keep fumbling. It's not going to be 24-0 like a few weeks ago, but I would give the Jaguars better than even odds of sweeping the season series here.

Snellings: I was going to say Vikings -3 over the Dolphins, but Doug beat me to it. So, I'll say Bengals and Saints under 43 points. These are two strong defenses and two thus far underwhelming offenses. The Bengals and their opponents have yet to combine for more than 43 points in any game this season, and they're averaging a combined 39.4 PPG in those five contests. The Saints have had two straight good scoring games, one against an extremely generous Seahawks defense that had absolutely no interest in tackling Taysom Hill and the other an unusual game in Europe against the Vikings. But in the two games before that, the Saints had averaged only 12 PPG and combined with their opponents to average 33 total points scored.

Marks: I'm going back to the well for a second straight week. Seattle (+1) first half vs Arizona. The Cardinals have been outscored 38-0 in the first quarter this season. Seattle has scored in over 60% of their first half possessions. Marinate in this ... the Seahawks are second in yards per play (behind the Bills), and rank in the top three in rushing and passing offense. They averaged eight yards per play last week against a much better Saints defense -- and put up 32 points (19 in the first half).

What is your favorite player prop?

Schatz: Let's go with Eno Benjamin over 77.5 rushing and receiving yards combined. With James Conner ruled out, Benjamin will be the workhorse against a Seahawks defense that ranks 24th in run defense DVOA and gives up over 50 receiving yards per game to opposing running backs so far this year.

Dolan: Kyler Murray over 27.5 rushing yards. The Seahawks allow the most yards per game and are especially terrible against the run, ranking dead last. Murray has averaged 27 rushing yards per game this season.

Moody: Marquise Brown over 69.5 receiving yards. Since moving to Arizona, Brown has emerged as Kyler Murray's top receiver. His connection to Murray, with whom he played college ball at Oklahoma, is part of the reason for this. In the last three games, Brown has averaged 9.3 targets and 102 receiving yards. This season, the Seahawks defense allows the seventh most passing yards per game. It will be Brown's final game before DeAndre Hopkins returns from suspension. He'll have a monster game against Seattle in a game that has a line of 50.5 points.

Marks: Tom Brady over 276.5 passing yards (-115). Brady owns the Steelers with a 12-3 record. He sports a 112 passer rating, averages over 280 passing yards a game and has tossed 34 touchdowns against this franchise. TJ Watt is still out with an injury, Brady's offense has been improving each week, and the Steelers secondary has been very kind to opposing wide receivers.

Walder: Tyler Higbee under 54.5 receiving yards (-120). This is an awfully high line for a non-elite tight end. I can see how it ended up here; Higbee has been an absolute target machine. But here's the thing, those targets are coming with an average depth of just 3.48 yards. Even if the ball keeps coming his way, he's going to need a ton of targets or some serious YAC to hit the over.