After an electrifying preseason, the stage is set for the NFL Opening Weekend 2025 to deliver even bigger upsets. With divisional grudge matches like the Chiefs vs. Chargers in Brazil, these games serve as the perfect backdrop for statement wins on the road to Super Bowl LX. But which teams will rise to the occasion?
Check out our 2025 NFL predictions and odds for every Opening Week match to sharpen your bets!
Table of Contents
Note: All odds are accurate as of Sept. 1 and subject to change.
Philadelphia Eagles vs. Dallas Cowboys
The Eagles (-360) are heavy favorites and expected to pull ahead late for a comfortable margin against the Cowboys (+280). In addition to dual-threat QB Jalen Hurts, the Super Bowl LIX champs have a strong defensive line. It’s anchored by DT Jalen Carter and LB Nolan Smith, who are expected to disrupt rival QB Dak Prescott.
Kansas City Chiefs vs. Los Angeles Chargers
The Chiefs (-170) are expected to win their neutral-site clash against the Chargers (+145) in Brazil. While both teams reshuffled their offensive lines, the Chiefs’ historical dominance closing out divisional games, coupled with star QB Patrick Mahomes’ impressive 7-2 record against rival QB Justin Herbert, tilts the odds their way.
Tampa Bay Buccaneers vs. Atlanta Falcons
The Buccaneers (-140) are close favorites against the Falcons (+120), who enter the Opening Week as 2.5-point home underdogs. The Bucs had a strong offense last year, climbing from 18th to 11th in total DVOA. That said, Atlanta still swept them and won four of five home openers, setting up for a tight divisional game.
Cincinnati Bengals vs. Cleveland Browns
The Bengals (-250) are strong favorites against the Browns (+210), backed by an explosive offense: QB Joe Burrow and WRs Ja’Marr Chase and Tee Higgins. While Cincinnati’s defense can be leaky (allowing 348.3 yards per game in 2024), their raw offensive power outweighs Cleveland’s questionable attack fronted by QB Joe Flacco.
Miami Dolphins vs. Indianapolis Colts
The Colts (-125) have a slight edge over the Dolphins (+105). Both teams enter with key playmakers, but Indianapolis’ upgraded secondary against Miami’s WRs Tyreek Hill and Jaylen Waddle is a notable strong point. The spread sits at 1.5, and with the total at 46.5, this matchup could turn out to be a shootout.
Las Vegas Raiders vs. New England Patriots
The Patriots (-145) are home favorites over the Raiders (+125), but only by a narrow margin. Uncertainty around New England’s rebuilt offense aside, their defense remains a strong anchor. Still, DE Maxx Crosby’s matchup against rookie LT Will Campbell could tilt momentum and pressure QB Drake Maye in the red zone.
Arizona Cardinals vs. New Orleans Saints
The Cardinals (-280) are clear 6.5-point favorites against the Saints (+230) in the Opening Week. The titanic trio of dual-threat QB Kyler Murray, WR Marvin Harrison Jr., and TE Trey McBride (one of the NFL’s top young players) form the nucleus of Arizona’s strong offense, pointing to them controlling both sides of the ball.
Pittsburgh Steelers vs. New York Jets
The Steelers (-150) are predicted to beat the Jets (+130) in what may be the season’s biggest revenge game. Four-time MVP Aaron Rodgers debuts as Pittsburgh’s QB, aided by WR D.K. Metcalf and rookie RB Kaleb Johnson. While the Jets could counter with a strong run game, the odds lean to Rodgers and a dominant pass rush.
New York Giants vs. Washington Commanders
The Commanders (-260) are 6.5-point home favorites over the Giants (+215). QB Jayden Daniels and WR Terry McLaurin headline a strong offense that averaged 28.5 PPG in 2024 (5th overall). In contrast, New York’s attack remains a concern after surrendering 48 sacks last year, putting Washington ahead in the odds.
Carolina Panthers vs. Jacksonville Jaguars
The Jaguars (-165) are favored over the Panthers (+140), with a 47.5 total hinting at a possible shootout. QB Trevor Lawrence and Jacksonville’s receiving corps should exploit defensive gaps, while Bryce Young aims to end Carolina’s run of six consecutive seasons of double-digit losses (29-71 since 2019).
Tennessee Titans vs. Denver Broncos
The Broncos (-400) are decisive favorites against the Titans (+300) with a -7.5 spread. Denver won 10 games last season, while Tennessee finished 3-14 and posted the worst ATS record in the league. Rookie QB Cam Ward could make an upset, but the odds point to a comfortable home victory.
San Francisco 49ers vs. Seattle Seahawks
The 49ers (-135) are slightly favored over the Seahawks (+115) despite Seattle’s home-field advantage. San Francisco’s Super Bowl hopes ride heavily on QB Brock Purdy and RB Christian McCaffrey leading the offense, while DL Nick Bosa anchors the defense. Expect a close game and possible upsets!
Detroit Lions vs. Green Bay Packers
The Packers (-140) are favorites against the Lions (+120). Green Bay ranked 3rd in total DVOA at 24.5% in 2024, led by Jordan Love under center. QB Jared Goff and Detroit’s passing attack could exploit a secondary that had some struggles last year, making this likely the NFC North’s closest rivalry.
Houston Texans vs. Los Angeles Rams
The Rams (-135) have a slight edge over the Texans (+115) as 2.5-point home favorites. Houston will lean on QB C.J. Stroud without injured RB Joe Mixon, while LA’s success hinges on Matthew Stafford’s health. If Stafford is sharp, expect WRs Puka Nacua and Davante Adams to tip the balance toward the Rams.
Baltimore Ravens vs. Buffalo Bills
Both the Ravens and Bills are equally priced at -110 (a true pick’em), with the odds reflecting genuine uncertainty. Baltimore ranked 1st in overall DVOA at 41.4% last season, led by QB Lamar Jackson’s MVP-caliber play, while QB Josh Allen and the Bills rode a 10-game home win streak. This matchup is an early AFC Championship preview.
Minnesota Vikings vs. Chicago Bears
The Vikings (-135) are 1.5-point road favorites over the Bears (+115) with a 43.5 point total. Minnesota’s roster appears stronger overall, with rookie QB J.J. McCarthy expected to play a careful, turnover-free game behind a steady run attack. Chicago leans on Caleb Williams, but his chemistry with the overhauled offense remains a concern.
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