Week 1 NFL Betting Odds: Lines, Preview, And Picks For Each Game

Written By Brian Sausa on September 12, 2021 - Last Updated on September 14, 2021

The calendar has flipped to August and training camp is now open across the National Football League. We are less than a month away from kicking off the 2021 NFL season, and there’s no better time to begin handicapping the opening week’s schedule.

While all odds aren’t yet released, we do have a moneyline, point spread, and total for every game on the slate at many different online sportsbooks across the United States.

Read below for odds, a betting preview, and predictions for every game on the Week 1 NFL schedule.

Week 1 NFL betting lines

NFL Week 1 matchups and predictions

Thursday, Sept. 9 (8:20 p.m. ET)

Dallas Cowboys at Tampa Bay Buccaneers (, O/U )

The 2021 season opens on Thursday, Sept. 9 with the Super Bowl champion Buccaneers playing at home, which is also the site where they lifted the Lombardi Trophy in February. Coming to town as underdogs are the Dallas Cowboys, a team that hopes to compete for an NFC playoff spot.

Honestly, the distraction of coronating a Super Bowl makes us want to take the visiting Cowboys with about a touchdown’s worth of free points. With that said, Dak Prescott is unlikely to see any preseason action at this point. He’s coming off a surgically-repaired ankle and has been dealing with a shoulder strain during camp. We’re hard-pressed to put any money on Dallas without seeing him play. Zach Martin, perhaps the most important player on the offensive line, is also out of action.

The Bucs do have a better roster top-to-bottom, particularly on the defensive side of the ball. It may not take more than a few stops to put the Cowboys behind too far to come back if Prescott isn’t as sharp as we’d hope he is.

Pick: Under 52 or higher (-110 or better), down to 51.5
Lean: Tampa Bay Buccaneers -7.5 (-110 or better)

Full Cowboys vs. Bucs Betting Preview

Sunday, Sept. 12 (1 p.m. ET)

Seattle Seahawks at Indianapolis Colts (, O/U )

The new-look Colts will open the regular season at home against Russell Wilson and the Seahawks. While Seattle opened as 2.5-point underdogs, the line has since flipped and the road ream is now the favorite by a couple of points with about two weeks until kickoff.

The season hasn’t even started, but there’s already drama in Indy. Carson Wentz is reunited with Frank Reich but foot surgery a few weeks back put his status in question for this game. As it turns out, Wentz is a go for Week 1, and so is Quenton Nelson on the offensive line.

Despite the many doubters, we are ready to back Wentz for a bounce-back season. Indianapolis is a team to watch out for in the AFC if it can staty healthy, and it all starts with the quarterback. Seattle has never been the same team on the road that it is at home, and the Colts have one of the deepest rosters in the NFL, including an improving defense. If Indy is going to be getting points, we’re taking them. But we also like home team to win straight up, and the lean is toward the under.

Pick: Indianapolis Colts +3 (-120 or better), Colts ML (+115 or better)
Lean: Under 50 (-110 or better), play down to 48 points

Full Seahawks vs. Colts Betting Preview

Pittsburgh Steelers at Buffalo Bills (, O/U )

Buffalo and its explosive offense is coming off an appearance in the AFC title game and is looking to establish itself as a contender once again. They’ll be favorites of almost a touchdown against the Steelers and their elite defense, though the total is set pretty high for these two teams.

Mike Tomlin’s clubs have an excellent track record when it comes to covering the spread as an underdog, so that’s one thing to keep in mind. That said, Buffalo averaged 30 points per game at home in 2020, good for third in the NFL. They’re going to score on Pittsburgh and it’s going to be up to Big Ben to keep up. We’d look toward the over here and if this gets to seven or more, there’s enough points of cushion to back the visitors.

Pick: Steelers +7 or better (play up to -120)
Lean: Over 48.5 (-110 or better)

Full Bills vs. Steelers Betting Preview

San Francisco 49ers at Detroit Lions (, O/U )

New Lions head coach Dan Campbell and quarterback Jared Goff debut together as underdogs against San Francisco at Ford Field. The 49ers lost both coordinators in the offseason but still have Kyle Shanahan at the helm and a much more talented roster than Detroit.

San Francisco opened as the largest favorite of the opening week (-7) and despite being on the road, there should be nothing wearing about the Niners. They should win, though beware of the hook as the spread has grown to -7.5. We’d snag seven to at least cover the key number on a push, even if it costs a few cents more. But looking at the Week 1 card, there are so many other way to go with your money.

Pick: Over 45.5 (-110 or better), play up to 46
Lean: San Francisco 49ers -7 or better (play up to -120)

Full 49ers vs. Lions Betting Preview

Los Angeles Chargers at Washington Football Team (, O/U )

The Washington Football Team looks to build on its NFC East title from last season, even if they did only win seven games in the process. Ryan Fitzpatrick currently sits atop the depth chart at QB and on the other side will be Justin Herbert, the 2020 offensive rookie of the year. Despite being on the opposite side of the country with a new head coach, Los Angeles opened as the slight favorite.

This will pit an elite WFT defense against a dynamic Chargers offense. We want to side with the away team’s talent level on the short line, but Los Angeles is installing a new offense and have a coordinator who is calling plays for the first time. The public may be all over Los Angeles and if this was Week 6, maybe we would be too. But we’ll take an established defense and the veteran Fitzpatrick to start the season hot. If you’re siding with Washington, may as well take the moneyline and forego the single point. The WFT is also a good add to a Stanford Wong six-point teaser, especially if you can get them to +7.5 or higher.

Pick: Washington Football Team +1.5 (-110 or better), Washington ML (-105 or better)
Lean: Under 44.5 (-110 or better), play down to 44 points

Full Chargers vs. WFT Betting Preview

New York Jets at Carolina Panthers (, O/U )

You couldn’t draw up a storyline better than this one. After trading Sam Darnold to Carolina in the offseason, the Jets are taking on their former QB in the opening week of the season. Under center for Gang Green will be Darnold’s replacement, No. 2 overall pick Zach Wilson. For what it’s worth, Wilson has looked somewhat decent in the preseason, though this will be his first game action in the NFL.

The Panthers opened as 4.5-point favorites and that number may only grow as the game nears, though it has held steady for now. Christian McCaffrey back in the fold and healthy for Carolina and this is the more talented team, plus it’s not their first game with a new head coach. We’d pick the Panthers to cover and another thing we definitely like here is the over 43.5, especially given how Wilson and the Jets’ No. 1 offense has looked in preseason.

Pick: Carolina Panthers -4 (-110 or better)
Lean: Over 43.5 (-110 or better), up to 44

Full Jets vs. Panthers Betting Preview

Philadelphia Eagles at Atlanta Falcons (, O/U )

The Eagles and Falcons will both have head coaches making their debuts in Week 1. Nick Sirianni and the Eagles will roll with Jalen Hurts under center for a new-look offense, while Arthur Smith begins the post-Julio Jones era in Atlanta. With these two teams in similar boats from a leadership standpoint, the spread opened at Falcons -3.5 and has held steady throughout the preseason.

This may not be the case later in the season, but the Falcons are set up well for Week 1. Both teams have new coaches taing over, but Smith gets the far more talented group. Atlanta’s defensive front is terrible and the Eagles should have some success with a healthy offensive line, but it’s the other side of the ball that makes this decisions for us. Philly ranked 24th in DVOA against the pass last season and beyond Darius Slay, are lacking depth in the defensive backfield. Even without Jones, Matt Ryan still has Calvin Ridley and Kyle Pitts as his top two targets.

The hook is going in the wrong direction, but we lean toward Atlanta scoring enough to cover the 3.5 points. If you’re unsure, either buy the half-point or consider adding the Eagles to a 6.5-point teaser to cover the key nubmers of seven and 10. As for the total, we like anything under 48 at -110 or better, and up to -120 if you can get 48.5.

Pick: Atlanta Falcons -3 (-110 or better)
Lean: Under 49 Points (-110 or better), down to 48

Full Eagles vs. Falcons Betting Preview

Jacksonville Jaguars at Houston Texans (, O/U )

There are already rumblings of unhappiness with Urban Meyer in Jacksonville, which isn’t what you want before even playing a single game. The good news for the Jags is that No. 1 overall pick Trevor Lawrence gets to make his debut against the Texans. Houston was already in a rebuild and is likely to have Tyrod Taylor under center to go with a severely undermanned roster at several positions.

There are far more questions than answers surrounding the Texans, who have a new GM and head coach in 2021 in addition to the QB situation. Houston’s offense won’t be able to take advantage of the Jags’ awful defense, and Lawrence will do just enough against another one of the league’s worst defensive units.

Pick: Over 45 (play up to -115)
Lean: Jacksonville Jaguars ML (-150 or better)

Full Jaguars vs. Texans Betting Preview

Minnesota Vikings at Cincinnati Bengals (, O/U )

The Bengals opened as 3.5-point underdogs at home against Minnesota in Week 1 but are expected to have QB Joe Burrow back following his ACL injury last year. Joining him on the Cincinnati offense is his old running mate and top-five pick Ja’Marr Chase. They face a prolific Vikings offense with another former LSU star in Justin Jefferson and game-breaking RB Dalvin Cook.

Minnesota ranked eighth in total offensive DVOA in 2020 behind a versatile attack on the ground and through the air. Cincinnati struggled mightily against the pass last season and with Jefferson and Adam Thielen out there, we could see some more of that in Week 1. Burrow’s first game back in almost a year is sure come with a few bumps in the road. If this were a month into the season, Cincinnati and the points feels like a worthwhile play. But as a Week 1 matchup, Minnesota may have an extra advantage.

Pick: Minnesota Vikings -3 (-110 or better), play up to -4
Lean: Over 47 (-110 or better)

Full Vikings vs. Bengals Betting Preview

Arizona Cardinals at Tennessee Titans (, O/U )

The AFC South champion Titans are hosting the Cardinals as slight favorites to open the season, and this is one of the more intersting Week 1 matchups. Arizona found itself on the precipice of the postseason last year but came up short, as Tennessee did against Baltimore in the Wild Card round.

The Cardinals are a trendy pick in the uber-competitive NFC West with Kyler Murray throwing to DeAndre Hopkins from behind what appears to be an improved offensive line. Not an easy matchup for Tennessee’s new defensive coordinator. Arizona’s defense also has some upside but whether or not we see that against Tennessee remains to be seen.

The Titans are geared up to have a prolific offense after adding Julio Jones to a unit that was already pretty explosive. Ryan Tannehill’s group ranked fourth in total DVOA and can control huge chunks of the game by employing Derrick Henry on the ground.  That combined with the Arizona defense being a work in progress has us leaning toward the home team in this one.

In the end, this game feels like it should have a ton of points. The only thing that would make us think otherwise is the fact that all eight of Arizona’s road games went under the total last season. That streak will eventually end, and there’s no better time than in Week 1. Considering the offenses for both teams, that would be our favorite play on this one.

Pick: Over 51 (-110 or better), play up to 52.5
Lean: Tennessee Titans -3 (-110 up to -120)

Full Cardinals vs. Titans Betting Preview

Sunday, Sept. 12 (4:25 p.m. ET)

Cleveland Browns at Kansas City Chiefs (, O/U )

In perhaps the most highly-anticipated game of the week, the Browns will travel to Arrowhead to play the Cheifs. This matchup will bring back memories of the AFC playoffs and Patrick Mahomes’ injury, plus the near-upset for Cleveland. The Browns look to build on their first playoff appearance since 2002 while AFC champion Kansas City dusts itself off following the Super Bowl defeat and enters the season as the favorite once again. This total opened as the highest of Week 1.

Both of these teams can put up points and if we’re talking about roster depth, Cleveland actually has Kansas City covered. But situationally, the Chiefs can still exploit the Browns with the early-down pass. No team passed on first and second downs in 2020 than Kansas City, and the success rate was one of the best in the league as well. The Browns’ defense faced plenty of these situations and struggled, which leads us to think Kansas City will have plenty of third-and-shorts to convert.

That said, the truth is that the Chiefs don’t do a great job of covering spreads. Kansas City was 6-2 at home last year but only covered in three of those games. In the second half of 2020, this group covered one game. Take Cleveland to cover and if you want to cover some key numbers, put the Browns in a teaser.

Pick: Cleveland Browns +6 (-110 or better)
Lean: Over 53 (-105 or better)

Full Browns vs. Chiefs Betting Preview 

Denver Broncos at New York Giants (, O/U )

When the Broncos visit the Giants at MetLife Stadium to begin the season, they’ll do so with Teddy Bridgewater under center rather than Drew Lock. Bridgewater really does feel like the perfect game-managing option for defensive-minded Vic Fangio and a team that is probably going to win with its defense first and foremost.

Denver opened at -1 but have recently climbed all the way up to -3 at some sportsbooks, though there area few -2 options out there still. We’re not sure whether an average team with a new quarterback traveling cross-country for Week 1 as a favorite is a good sign for the Broncos or a bad sign for the Giants. Either way, defense travels and Denver plays it. Even with some new weapons on the field for Daniel Jones, Saquon Barkley may not be back yet and that’s a huge void. If Barkley is indeed out, we’re taking the Broncos and the under.

Pick: Denver Broncos -2 (-110 or better), play up to -2.5 (-110)
Lean: Under 43 (play up to -120)

Full Broncos vs. Giants Betting Preview

Green Bay Packers at New Orleans Saints (, O/U )

After a tumultuous offseason, the Green Bay Packers start things off on the road against the Saints in the Superdome. It looked for a while like the Packers would look different at the QB position this year, but Aaron Rodgers is back and so is Davante Adams. The biggest question marks come from what to expect from Jameis Winston, although he shined in preseason.

There’s little doubt that Winston will be better this time around compared to his days in Tampa, but I still expect to see a few careless mistakes that could come back to haunt the Saints. There’s also the subject of Rodgers, who is absolutely going to play with a chip on his shoulder after everything that has happened. Very few players elicit backing from bettors based on non-numberical or gambling factors, but Rodgers is one of them. at three points or less, we’re on Green Bay in the opener.

Editor’s Note: A major factor here is the fact that New Orleans won’t be playing any true road games, and this matchup will take place in Jacksonville. It has caused the line to jump since the time of this article’s original publish date. We’d still consider a bet on Green Bay up to -6 (-110 based on the situation).

Pick: Green Bay Packers -3 (-110 or better)
Lean: Over 50 (play up to -115)

Full Packers vs. Saints Betting Preview 

Miami Dolphins at New England Patriots (, O/U )

An AFC East rivalry resumes immediately as the Patriots host the Dolphins in Foxborough in Week 1.New England opened at -2 but as the offseason has progressed, the spread began to grow a bit as some wholesale changes are being made on the Pats’ roster.

The Patriots managed to go 7-9 despite injuries and a lack of roster talent, but things are very different now.  Added to the offense are tight ends Jonnu Smith and Hunter Henry, along with a host of defensive pieces. Oh, and Cam Newton is gone as Mac Jones takes the reins as a rookie after a stellar preseason.

The Dolphins have one of the deepest rosters in the NFL. They managed to hold onto All-Pro cornerback Xavien Howard and return one of the best scoring defenses in the league. Miami also added two weapons in the first round of the draft to help out Tua, who we should see improve in year two.

That said, we need to back New England here. The Patriots have won five of the past six season openers and even though this is a different team, there’s one thing that remains the same. Nobody feasts on young quarterbacks the way Bill Belichick does and he’s also one of the coaches with a winning track record with time to prepare. We may very well see an improved Tua, but we aren’t likely to see it in Week 1.

As for Jones, his first NFL action is agisnst a tough defense. With that said, he showed enough poise in the preseason that a competent game plan should see him through. At a field goal or less, we are fine with taking the Patriots to open up the season with a win and a cover. Three points may be a push number, but there are currently plus-odds out there and that could be worthwhile.

Pick: New England Patriots -2.5 (-120 or better), play up to -3 (-110 or better)
Lean: Under 45 (-110 or better)

Full Dolphins vs. Patriots Betting Preview 

Sunday, Sept. 12 (8:20 p.m. ET)

Chicago Bears at Los Angeles Rams (, O/U )

The first Sunday Night Football matchup of the year will feature the Rams hosting the Bears at SoFi Stadium, which welcomes fans for a regular-season game for the very first time. There aren’t many spreads of a touchdown or more in Week 1 but Los Angeles opened at -7 and the spread has stuck there at most online sportsbooks.

There are question marks for both of these teams, starting with who the Bears start at quarterback. It looks like it will be Andy Dalton in the beginning despite the clamoring for Justin Fields, though the Bears’ offensive line is probably more worrisome than the quarterback. Los Angeles has a new defensive coordinator in Raheem Morris but return one of the best units in the league. On offense, it has an upgrade at quarterback in Matthew Stafford.

All things considered, it’s hard not to be comfortable with the home team here. The Rams will finally have fans in the building and are upgraded at the QB position while still boasting what’s probably a top 10 offensive line. A whole touchdown is plenty of points so if you’re unwilling, put them in your Stanford Wong six-point teaser.

Despite the Rams’ defense potentially being due for regression, the Chicago offense is unlikely to keep up with Dalton unless its defense carries the day. At seven points or less, we’ll go with the Rams at home and a likely under on this mid-40s total.

Pick: Los Angeles Rams -7 (-110 or better)
Lean: Under 45 (-110), play down to 44

Full Bears vs. Rams Betting Preview 

Monday, Sept. 13 (8:15 p.m. ET)

Baltimore Ravens at Las Vegas Raiders (, O/U )

The Monday Night Football schedule opens with one game rather than the pair we’ve been accustomed to as Baltimore visits Las Vegas and fans are welcomed to Allegiant Stadium for the first time. Batimore opened at -4.5 and the number hasn’t budged much from there, while the total is at 51 points.

One thing feels certain: there should be scoring in this game. Las Vegas home games were 7-1 to the over in 2020, aided by the Raiders allowing the third-most points in the league. Despite Baltimore’s elite defense, the Las Vegas offense scored at least 20 points in every home game last season. So we like the over, but beware of any number over 50 points. All of the injuries and some late movement would tell us to lay off at this number, however.

Baltimore is a rare team that ranked top 10 in scoring offense (9th) and defense (1st) during the 2020 regular season. While last year has no bearing on this one, enough of the personnel and coaching is the same for us to lean on what we already know about these teams. The Ravens are a more well-rounded group and until we see improvement on the Las Vegas defense, we’re siding with Baltimore, even with all the injuries.

Pick: Baltimore Ravens -3  (buy up to -120)
Lean: Over 50 points (play up to -115) 

Full Ravens vs. Raiders Betting Preview

*all odds are subject to change

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Brian Sausa

Brian Sausa is a longtime sports content creator with extensive betting experience and knowledge of the industry. A journalism graduate with a ranging sports background, Brian has been employed by multiple professional leagues including MLB, MiLB, and the NHL.

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