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NFL Week 1 Picks, Betting Predictions & Best Bets To Back

Bill Speros for Bookies.com

Bill Speros  | 33 mins

NFL Week 1 Picks, Betting Predictions & Best Bets To Back

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The NFL betting season is finally here. We made it. That means it is time to make some NFL Week 1 picks. We cashed in a big way on opening night, grabbing the Bills ATS vs. the LA Rams at SoFi. Buffalo easily covered in a 31-10 victory over the defending Super Bowl champions.

But what about the rest of the Week 1 NFL schedule? We have NFL Week 1 picks right here for every game on the slate. The offseason saw a cataclysmic change with 10 new coaches, Matt Ryan and Russell Wilson swapping conferences, and the return of Tom Brady after a 40-day “retirement.” It makes for some challenging NFL Week 1 best bets.

RELATED: NFL Week 1 Odds, Betting Lines and Analysis For Every Game

The Rams were completely outplayed by the Bills on Thursday Night Football, as Buffalo underlined its credentials as the preseason Super Bowl favorite. While the Bills covered (-2.5), the total (52) went way under as both offenses struggled with turnovers. The highest Over/Under on Sunday belongs to Chiefs vs. Cardinals (53.5) in Glendale, Arizona, the site of Super Bowl 57.

The Bills saw their playoff run cut short last year in the Divisional Round by the Chiefs. In that game, 25 points were scored in the final 3 minutes of regulation before the Chiefs won the OT coin toss (never call tails, Josh Allen) and the game, 42-36. That outcome triggered an NFL rule change that guarantees both teams one possession in overtime, even if the first team with the ball scores a touchdown. On Thursday's evidence, Allen and his Bills are ready to roll right back to the playoffs.

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Underdogs Hold Early-Season Edge

Last year, the underdogs took a sizable lead early in the season when it came to covering ATS. Oddsmakers at betting apps are keeping things tight early in the 2022-23 season. Only one game on the Week 1 schedule carried a line greater than 7 points (the Colts opened at -8 against the Texans but it's now around -7.5). There are nine games with home underdogs

Von Miller, who returned to LA as a Bill and registered two sacks on Thursday, is not the only big-name player who is starting the new season against his old team. Wilson and the Broncos visit Seattle on Monday night in Week 1. Wilson played for the Seahawks for 13 seasons before he was dealt to the Broncos in a QB swap. 

The NFL pushed Wilson’s return to Seattle to the top of the schedule pile because of concerns that the Seahawks could be among the worst teams in the NFC and Wilson’s time in Seattle will be the focus of much of the offseason hype. Wilson's Broncos are -6.5 point favorites over the Seahawks. The line opened at Broncos -4, which was a great price for those that jumped on to make their week 1 NFL best bets then.

The RedZone Octo-Box won’t be enough for the early slate, as there are nine games in Week 1 that begin at 1 p.m. ET on Sunday. The marquee 4:25 p.m. ET games have the Packers visiting NFC North rival Minnesota and the Raiders facing off against the host Chargers. Not to mention, the Chiefs heading to Arizona. We can't wait for the action to begin.

Now it’s on to our Week 1 NFL picks to back on your sports betting app: 

NFL 2022 Season Week 1 Picks

DateMatchupWeek 1 Picks
Thursday, Sept. 8Bills @ Rams Locked In Bills +1 ATS
Sunday, Sept. 11Ravens @ Jets Jets +7 ATS
Sunday, Sept. 11Eagles @ Lions Lions +4.5 ATS
Sunday, Sept. 11Steelers @ Bengals Bengals -6.5 ATS
Sunday, Sept. 11Saints @ Falcons Under 42.5
Sunday, Sept. 11Jags @ Commanders Locked In Jags +4 ATS
Sunday, Sept. 1149ers @ Bears Locked In Under 42.5
Sunday, Sept. 11Colts @ Texans Locked In Colts -7 ATS
Sunday, Sept. 11Patriots @ Dolphins Locked In Pats +3.5 ATS
Sunday, Sept. 11Browns @ Panthers Over 41.5
Sunday, Sept. 11Packers @ Vikings Packers -1.5 ATS
Sunday, Sept. 11Giants @ Titans Under 43.5
Sunday, Sept. 11Raiders @ Chargers Raiders +3.5 ATS
Sunday, Sept. 11Chiefs @ Cardinals Under 53.5
Sunday, Sept. 11Bucs @ Cowboys Locked In Cowboys +2.5 ATS
Monday, Sept. 12Broncos @ Seahawks Locked In Broncos -5 ATS

All picks accurate as of publication (Sept. 10) and subject to change.

Thursday, Sept. 8

Buffalo Bills at Los Angeles Rams, 8:20 p.m. (NBC)

The “Battle of the Seans” serves as the NFL season-opener and a potential Super Bowl 57 preview. Sean McVay and Sean McDermott will determine “Sean” coaching bragging rights now that Sean Payton has stepped aside in New Orleans. 

Things only get tougher for the Rams. In addition to the season-opener against the Bills, the Rams have Dallas at home and return to Tampa Bay, where they eliminated the Bucs in the playoffs last year. The Rams catch a break in terms of having the full offseason to prepare for the Bills, but this game has all the makings of a big-time letdown for the home team. Oddsmakers have moved this line more than 3 points. You've missed your chance to grab the Bills as underdogs as one of your NFL Week 1 picks - at one point they were available at +1 but they're now -2.5 on the spread.

Best Bet: We locked in several weeks ago with the Bills +1 at -115 with DraftKings . The Bills covered with a 31-10 victory in LA.

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Sunday, Sept. 11

Baltimore Ravens at New York Jets, 1 p.m. (CBS)

The Jets begin the season in a familiar place – as a home underdog. Last season, Gang Green went 4-13 overall but managed to go +2 ATS. Four of the Jets' six covers came at home. Week 1 is usually the closest the NFL gets to opposite world, so keep an eye on the Jets here to win this one outright, once again ruining their chance for the first overall pick. 

Zach Wilson has legit weapons at receiver, tight end and running back (including second-round draft pick Breece Hall) after a busy offseason, but he's out for Week 1 with a knee injury. Instead, it will be former Ravens QB Joe Flacco, who could be starting for up to four weeks as Wilson recovers. It remains to be seen if Wilson gets his job back.

This line has moved significantly toward Baltimore in recent weeks, given the positive news concerning Lamar Jackson and the injury to Wilson. Still, we like the Jets ATS as one of our NFL Week 1 picks for Sept. 11. Flacco might actually give them a better shot here and the Ravens are giving them a full TD.

Best Bet: Jets +7 at -110 with DraftKings  

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Philadelphia Eagles at Detroit Lions, 1 p.m. (FOX)

The Lions were the surprising betting story of the 2021-22 regular season. Detroit went 11-6 ATS despite winning only three games outright. Both teams have quarterbacks who have the potential to be overwhelmed by the panoply of weapons at their disposal. The Lions drafted Alabama WR Jameson Williams and signed D.J. Chark this offseason. They join Amon-Ra St. Brown, tight end T.J. Hockenson, and running back D’Andre Swift as potential targets for Jared Goff, although Williams will miss Week 1 after tearing his ACL in the National Championship game against Georgia. 

In Philly, the Eagles landed WR A.J. Brown (via trade from Tennessee) to join WR DeVonta Smith and TE Dallas Goedert. Will Jalen Hurts flourish or flounder? Take the Lions to cover as one of your NFL week 1 picks for Sunday. This also has the markings of a Week 1 game that will be played in opposite land. Later in the season, the Eagles would win this one by 2 TDs. 

Best Bet: Lions locked in at +4.5 at -110 with DraftKings , while the line has since moved to Lions +5  

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Pittsburgh Steelers at Cincinnati Bengals, 1 p.m. (CBS)

These two long-time rivals open the season against each other for the first time ever in 2022. Their long-time historic roles are reversed this time. The Bengals are defending AFC North and AFC champions. QB Joe Burrow took a beating last season but nearly won the Super Bowl in just his second season. The Bengals bolstered their offensive line to make sure Burrow will still be ambulatory at age 30. 

The Steelers, meanwhile, begin the season without QB Ben Roethlisberger for the first time since 2003. Right now, their starting QB is veteran journeyman Mitchell Trubisky, who beat out first-round rookie Kenny Pickett during training camp. But by most accounts, Pickett improved after a slow start in camp and it might not be long before we see him in action. This should be a good early test for the Bengals O and its rebuilt O-Line.

Best Bet: Bengals -6.5 at -110 with BetRivers

RELATED: Best NFL Week 1 Parlay Bets To Back

New Orleans Saints at Atlanta Falcons, 1 p.m. (FOX) 

This game includes one of the 10 new head coaches in the NFL this season. Former Raiders head coach and Saints DC Dennis Allen is the new boss in New Orleans after Payton stepped down. Jameis Winston is back as the starting QB for the Saints. Winston tore his ACL in the Saints' win over Tampa Bay last Halloween. The Saints also should have Michael Thomas back from a long-term ankle injury. He looked sharp in training camp, as did rookie WR Chris Olave. Alvin Kamara is also available.

Matt Ryan was traded by the Falcons to Indianapolis after 14 seasons in the ATL. Marcus Mariota is the new starting QB in Atlanta. Yikes. We locked this one in at under 42 earlier this summer as one of our NFL Week 1 best bets. It could be a long afternoon for the Falcons, with first-round rookie Drake London questionable to play.

Best Bet: Under 42.5 points at -110 at PointsBet

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Jacksonville Jaguars at Washington Commanders, 1 p.m. (CBS) 

New head coach Doug Pederson should bring leadership, maturity and stability to the Jaguars organization following the Urban Meyer Error. The Jaguars have earned the first pick in the last two NFL drafts. The Jaguars spent heavily in free agency, bringing in tight end Evan Engram from the Giants, WR Christian Kirk from the Cardinals, LB Foye Oluokun from the Falcons and CB Darious Williams from the Rams. They selected edge rusher Travon Walker with the first pick. Trevor Lawrence could have the same sort of sophomore success Burrow enjoyed last year, especially if Kirk turns into a legitimate WR1. This line has slid in Jacksonville's favor all summer. 

The Commanders finally have a name. They also have Carson Wentz at QB.

Best Bet: Locked in Jaguars +4 at -105 at PointsBet

San Francisco 49ers at Chicago Bears, 1 p.m. (FOX)

Trey Lance will be the starter for San Fran in Week 1, with Jimmy G his backup after the Niners failed to find a trading partner. Lance's leash could be very short because the 49ers know they can win with Jimmy G. The Bears hired Matt Eberfus as head coach. He brought in a new offensive and defensive coordinator. The 49ers reached the NFC title game before blowing a 10-point lead to the Rams. Deebo Samuel has agreed a new deal to remain by the Bay.

Considering the Niners will be getting Lance settled and Bears QB Justin Fields has nobody to throw to, we're liking the Under here as one of our favorite NFL Week 1 picks for Sunday. This could be a defensive slugfest between two teams struggling to score points.

Best Bet: Locked In Under 42.5 points at -110 with DraftKings  

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Indianapolis Colts at Houston Texans, 1 p.m. (CBS)

This is the biggest line of Week 1 for a reason. It's still not putting us off making Indianapolis one of our favorite NFL week 1 picks. The Colts could make a run at the AFC title. The Texans are on their way to the No. 1 pick in the draft. Matt Ryan makes his first start for the Colts against perhaps the worst team in the conference, if not the entire league. The Texans hired Lovie Smith to be their head coach after dumping David Culley. 

The Colts are primed to contend in the AFC South with Ryan under center. The Texans shipped QB Deshaun Watson to the Browns after a grand jury declined to indict Watson in relation to multiple civil sexual assault allegations. Second-year QB Davis Mills has emerged as the starter in Houston – for now. We locked in Indy at -7 early in the summer as one of our top Week 1 NFL best bets. This could be a big game for Jonathan Taylor.

Best Bet: Locked In Colts -7 at -110 with DraftKings  

RELATED: NFL Schedule Release: Best NFL Over/Under Win Totals To Bet Now

New England Patriots at Miami Dolphins, 1 p.m. (CBS)

Dolphins coach Mike McDaniel makes his NFL debut against Bill Belichick, who has eight Super Bowl rings and 321 victories as a head coach. No one is sure who will be calling the plays, but Patriots second-year QB Mac Jones has a new toy in former Dolphins WR DeVante Parker. The Dolphins swept New England last year but the Patriots historically have enjoyed success playing in Miami early in the season. Mac Jones was stellar during OTAs, and has leaned out and added muscle this offseason.

The Dolphins are all-in with Tua Tagovailoa at QB. That stability should help, along with the acquisition of Tyreek Hill from the Chiefs. The Dolphins were rattled this offseason when fired coach Brian Flores filed a racial discrimination lawsuit against the team and NFL, and alleged that owner Stephen Ross offered to pay him extra to lose games in 2019. With four months to prepare, Belichick should have the edge here. For our NFL Week 1 picks, we like the Pats and the points. Both of these teams face an uphill battle to unseat the Bills atop the AFC East, though.

Best Bet: Patriots +3.5 at -105 at PointsBet

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Cleveland Browns at Carolina Panthers, 1 p.m. (CBS)

How about this for an opportunity at immediate revenge? After beating out incumbent Sam Darnold for the starting QB gig, Baker Mayfield will be leading the Panthers against his old team in Week 1. Expect fireworks. 

The Browns guaranteed Deshaun Watson $230 million and are all-in on him as the future of their franchise, even though he's out of this Week 1 matchup. While Watson may be clear from a criminal perspective, he will be suspended for the first 11 games of the 2022 season. It looks likely to be Jacoby Brissett suiting up at QB in Week 1 for Cleveland, so expect a healthy dose of Nick Chubb and the Browns running game.

We expect Mayfield to come out slinging and for that reason we're going Over 41.5 as one of our NFL week 1 best bets. Christian McCaffrey also should have a big day for Carolina.

Best Bet: Over 41.5 points at -105 at PointsBet

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Green Bay Packers at Minnesota Vikings, 4:25 p.m. (FOX)

Look for FOX's Kevin Burkhardt to make his debut as their new lead NFL announcer in this game. Two-time defending NFL MVP Aaron Rodgers is back. But A-Rod is missing his favorite target in Davante Adams, who hit the jackpot with a trade to the Las Vegas Raiders. The Packers still have running backs Aaron Jones and AJ Dillon, who they'll likely lean on with Allen Lazard questionable to play. 

The Vikings will be breaking in a new coach in Kevin O’Connell and sit as a slight home underdog. Matt LaFleur has won 39 of his first 49 starts as an NFL head coach and should have the Packers ready. For our NFL Week 1 best bets, we jumped on Green Bay when they were 1.5-point favorites. You can still grab them there if you're quick.

Best Bet: Packers -1.5 at -110 with DraftKings  

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New York Giants at Tennessee Titans, 4:25 p.m. (FOX)

The Giants hired former Bills offensive coordinator Brian Daboll as head coach. Daboll is sticking with Daniel Jones at QB - for now. Kadarius Toney may finally be healthy, while rookie Wan'Dale Robinson looks locked in for the slot role. The Titans finished with the best record in the AFC but lost at home to Cincinnati 19-16 in the Divisional round after QB Ryan Tannehill threw three picks. 

The Titans still boast Derrick Henry as the centerpiece of their offense, but traded away AJ Brown to the Eagles. This game points to being an ugly, low-scoring affair. We snagged the under at 43.5 points for our NFL Week 1 picks on Sunday. You can still get that line at DraftKings and BetMGM, and we advise you do.

Best Bet: Under 43.5 Points at -110 with BetMGM  

RELATED: NFL Schedule Release: How Many Miles Will Your Team Travel In 2022?

Las Vegas Raiders at LA Chargers, 4:25 p.m. (CBS)

The AFC West is loaded this season. The Raiders hired Josh McDaniels as their new head coach, swiping the long-time Patriots offensive coordinator. Raiders QB Derek Carr has his former Fresno State teammate Adams as a new No. 1 target. The Raiders also added Chandler Jones, Demarcus Robinson and Bilal Nichols via free agency, while TE Darren Waller agreed a big new contract on Saturday. 

The Chargers bring back most of their key players and look to take the next step and reach the postseason with Justin Herbert under center. This Over/Under total (currently around 52.5) seems a bit too high for Week 1, but we’re going with the Silver and Black on the road and grabbed them at +4 when this line was set. The return of Darren Waller is also very encouraging for the Raiders, who could make a statement in the AFC West here. The line has moved a touch in the Raiders' direction ahead of Week 1.

Best Bet: Raiders +3.5 at -105 with DraftKings  

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Kansas City Chiefs at Arizona Cardinals, 4:25 p.m. (CBS)

Patrick Mahomes II no longer has Hill waiting at the receiving end of his long throws. The Chiefs will try to make up the loss of Hill with Marquez Valdes-Scantling and JuJu Smith-Schuster, plus copious targets for Travis Kelce. The Cardinals and QB Kyler Murray finally settled on a long-term deal after an offseason of contract strife. The Chiefs struggled early against the line in 2021 and at one point last year were 4-15 ATS. But we like the under here given the usual issues in Week 1, plus the absence of DeAndre Hopkins through suspension. 

Good news, Kansas sports betting fans because legal wagering is now live and you can make your NFL Week 1 picks ahead of Sunday. As far as best bets for NFL Week 1 on the Chiefs, we like the Under on this Cardinals matchup. The number (which opened at 54) is the highest of the week. The Chiefs have got very pricey on the spread, where they've moved from -3 all the way to -6 in the last few days. Hit 'Bet Now' below to access a special Chiefs Double Your Money offer at DraftKings for this weekend.

Best Bet: Under 53.5 points at -105 at PointsBet

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Tampa Bay Buccaneers at Dallas Cowboys, 8:25 p.m. (NBC)

These two teams began the 2021 season at Tampa Bay in a game won by the Buccaneers 31-29 on a last-second field goal. Tom Brady is back after a brief retirement, along with most of the big names on the Bucs. But Rob Gronkowski is not one of them after the future Hall of Fame tight end announced his retirement. The Bucs replaced Gronk with Kyle Rudolph at the top tight end spot. 

The Cowboys are mostly back intact. The biggest challenge for the Cowboys remains keeping Dak Prescott healthy. It’s rare that the Cowboys are home underdogs. Dallas had the best record in the NFL last year ATS, going 13-5 including the playoffs. The Bucs, meanwhile, absorbed significant amounts of cash from the betting public and covered just ten times despite winning 14 games. So, for that reason, we like Dallas here as one of our NFL Week 1 picks and locked them in at +2.5. They have floated between +1.5 and +2.5 over the past few weeks.

Best Bet: Cowboys +2.5 at -105 with DraftKings  

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Monday, Sept. 12

Denver Broncos at Seattle Seahawks, 8:15 p.m. (ABC/ESPN)

This game marks the Monday Night Football debut of announcer Joe Buck and play-by-play analyst Troy Aikman, both of whom left FOX to join ABC/ESPN. Russell Wilson’s homecoming will be the other overriding storyline heading into this game. The Broncos and Seahawks exchanged quarterbacks in the offseason, with Wilson leaving Seattle after 11 seasons and Drew Lock heading to Seattle. The Seahawks' over/under win total is just 6 games. 

The Broncos are solid on both sides of the ball. By the way, the Broncos, too, changed coaches in the offseason with former Green Bay QB coach Nathaniel Hackett taking over for Vic Fangio. It is difficult to think this will be anything other than a Broncos rout. Geno Smith beat out Lock for the starting gig in Week 1. The line keeps moving further in the Broncos direction. We snagged Denver at -5 as one of our NFL Week 1 picks. It's now around -6.5.

Best Bet: Locked in Broncos -5 at -110 with DraftKings  

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About the Author

Bill Speros for Bookies.com
Bill Speros
Bill Speros is an award-winning journalist and editor whose career includes stops at USA Today Sports Network / Golfweek, Cox Media, ESPN, Orlando Sentinel and Denver Post.