The NFL regular season kicks off September 4, 2025, with a full slate of 16 games running through Monday night. Bettors will see everything from double-digit favorites to coin-flip spreads under a field goal. Totals range from the low 30s to the 50s. Below are the betting lines and picks for many of the key Week 1 matchups.
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Dallas Cowboys at Philadelphia Eagles (Thu, Sep 4)
Odds: Eagles -7.5 | Total: 47.5
Philadelphia begins the season at home as a strong favorite. Dallas will need turnovers to keep it close. Opening night sets the tone for the NFC East.
Pick: Eagles -7.5
Kansas City Chiefs vs Los Angeles Chargers (Fri, Sep 5, São Paulo)
Odds: Chiefs -3 | Total: 45.5
The first NFL regular-season game in Brazil has Kansas City as a short favorite. Patrick Mahomes leads the Chiefs, while the Chargers look for consistency on both sides. Neutral site adds some variance.
Pick: Chiefs -3
Cincinnati Bengals at Cleveland Browns (Sun, Sep 7)
Odds: Bengals -5.5 | Total: 47.5
Joe Burrow and the league’s top passing offense return. Cleveland struggled to score in 2024 and still has quarterback uncertainty. The Bengals should control this one on the road.
Pick: Bengals -5.5
Pittsburgh Steelers at New York Jets (Sun, Sep 7)
Odds: Steelers -2.5 | Total: 37.5
This is the lowest total of the week. Pittsburgh relies on defense and a controlled run game. The Jets hope Aaron Rodgers can find answers, but points will be hard to come by.
Pick: Steelers -2.5, Under 37.5
Carolina Panthers at Jacksonville Jaguars (Sun, Sep 7)
Odds: Jaguars -3 | Total: 46.5
Jacksonville enters as a field-goal favorite at home. Bryce Young leads a Panthers offense looking to improve. The Jaguars’ balanced attack makes them the safer play.
Pick: Jaguars -3
Tampa Bay Buccaneers at Atlanta Falcons (Sun, Sep 7)
Odds: Buccaneers -2.5 | Total: 46.5
The Bucs open as short road favorites in this NFC South matchup. Atlanta will lean on the run game to stay in it. The line suggests a close finish.
Pick: Buccaneers -2.5
Arizona Cardinals at New Orleans Saints (Sun, Sep 7)
Odds: Cardinals -6.5 | Total: 42.5
Arizona is one of the bigger favorites of the week. The Saints have issues under center and must lean on defense. The Cardinals’ offense should be enough.
Pick: Cardinals -6.5
Green Bay Packers vs Detroit Lions (Sun, Sep 7)
Odds: Packers -2.5 | Total: 47.5
This NFC North matchup is lined under a field goal. The Lions lost key staff and players, while Green Bay added Micah Parsons and a new WR1. A tight divisional game is expected.
Pick: Packers -2.5
Baltimore Ravens at Buffalo Bills (Sun, Sep 7, SNF)
Odds: Bills -1.5 | Total: 51.5
This is the highest total of Week 1. Both offenses rank among the league’s best. Buffalo is a slight home favorite, but the Ravens are live to win outright.
Pick: Ravens +1.5, Over 51.5
Minnesota Vikings at Chicago Bears (Mon, Sep 8, MNF)
Odds: Vikings -1.5 | Total: 43.5
The week closes with a divisional game in Chicago. The Vikings are narrow road favorites. The Bears have value at home with a low total on the board.
Pick: Bears +1.5
Final Word – Week 1 Picks with WagerHome
Week 1 features a mix of heavy favorites and small spreads. The Eagles and Broncos are the only teams over a touchdown favorite, while games like Ravens vs Bills and Packers vs Lions project as coin flips. Totals range from the defensive 37.5 in Steelers vs Jets to the explosive 51.5 in Ravens vs Bills.
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