2026 NFL Odds & Predictions for Week 1: Can the 49ers Upset the Rams?

49ers rams predictions

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An upset in Australia headlines my NFL Week 1 odds and predictions. The 2026 season kicks off on Wednesday, September 9th, with all 32 franchises in action on opening week. 

Continue reading to see my favorite NFL picks for Week 1. I analyze the latest NFL odds and share my top picks for opening weekend, including why the 49ers have an excellent chance of taking down the Rams in Melbourne.

NFL Week 1 Odds Snapshot

Here are the top NFL odds for Week 1, courtesy of the best NFL sportsbooks

Week 1 MatchupLucky RebelBetUSBetOnline
New England Patriots vs. Seattle SeahawksPatriots (+160) 
Seahawks (-185)
Patriots (+155)
Seahawks (-180)
Patriots (+158)
Seahawks (-181)
San Francisco 49ers vs. Los Angeles Rams49ers (+185)
Rams (-225)
49ers (+175)
Rams (-205)
49ers (+177)
Rams (-205)
New Orleans Saints vs. Detroit LionsSaints (+260)
Lions (-320)
Saints (+253)
Lions (-305)
Saints (+249)
Lions (-305)
Cleveland Browns vs. Jacksonville JaguarsBrowns (+305)
Jaguars (-410)
Browns (+312)
Jaguars (-390)
Browns (+310)
Jaguars (-390)
Buffalo Bills vs. Houston TexansBills (-108)
Texans (-112)
Bills (Pk)
Texans (Pk)
Bills (Pk)
Texans (Pk)
Arizona Cardinals vs. Los Angeles ChargersCardinals (+380)
Chargers (-550)
Cardinals (+425)
Chargers (-550)
Cardinals (+415)
Chargers (-550)
Dallas Cowboys vs. New York GiantsCowboys (-160)
Giants (+135)
Cowboys (-160)
Giants (+138)
Cowboys (-161)
Giants (+141)
Denver Broncos vs. Kansas City ChiefsBroncos (+127)
Chiefs (-147)
Broncos (+120)
Chiefs (-140)
Broncos (+122)
Chiefs (-142)

The odds above are accurate and represent the best available prices from the listed sportsbooks as of September 4th, 2026. 

The Nerd’s Top NFL Picks for Week 1

See the table below for my favorite picks for Week 1 of the 2026 NFL season. 

MatchupBetOddsBookmaker
New England Patriots vs. Seattle SeahawksGeorge Holani anytime TD scorer +185Lucky Rebel
San Francisco 49ers vs. Los Angeles Rams49ers to beat the Rams+185Lucky Rebel
Cleveland Browns vs. Jacksonville JaguarsJaguars to beat the Browns-390BetOnline
Buffalo Bills vs. Houston TexansDavid Montgomery 64+ rushing yards+118BetUS
Dallas Cowboys vs. New York GiantsCowboys to beat the Giants-160BetUS
Denver Broncos vs. Kansas City ChiefsBroncos cover against the Chiefs+2.5 (+100)Lucky Rebel

Patriots vs. Seahawks

Seahawks
  • Verdict: Bet on George Holani to score a TD
  • Best captured price: Lucky Rebel lists Holani at +185 to score
  • Break-even probability: 35.09%
  • Target price: +115
  • Primary risk: Holani does not get goal-line touches as rumored.
  • Confidence: Moderate – Holani is unproven but will start the year as Seattle’s short-yardage back.

George Holani Anytime TD Scorer (+185)

Seattle relied heavily on its rushing attack to beat New England in the Super Bowl this past February. Kenneth Walker III left in free agency, and Zach Charbonnet is on the PUP list. 

Rookie Jadarian Price is set to be the RB1 for Seattle to begin the season. However, according to reports, Holani will serve as the short-yardage and goal-line back. Opportunities near the goal line increase Holani’s chances to score in the season opener. 

49ers vs. Rams

49ers linebacker Fred Warner
  • Verdict: Bet on the 49ers to win
  • Best captured price: Lucky Rebel has the 49ers as +185 underdogs
  • Break-even probability: 35.09%
  • Target price: Even money or shorter odds
  • Primary risk: Aaron Donald starts for the Rams.
  • Confidence: Low – San Francisco is the underdog, but their familiarity with the Rams opens the door for an upset.

San Francisco 49ers (+185)

The 49ers are 8-5 against the Rams since 2020 and left for Australia a week before LA did. Their extra rest will help San Francisco players acclimate and recover from jet lag after the long flight. 

Aaron Donald is making the trip, but it is unclear if he will play for LA. If LT Trent Williams can minimize Myles Garrett’s impact, the 49ers’ run-heavy scheme will help San Fran control the clock and pull off the upset. 

Browns vs. Jaguars

NFL
  • Verdict: Bet on Jaguars to win
  • Best captured price: BetOnline has Jacksonville as a -390 favorite
  • Break-even probability: 79.59%
  • Target price: -500 or shorter
  • Primary risk: Cleveland’s defense dominates the Jaguars offense.
  • Confidence: High – Jacksonville was a playoff team last year, and Cleveland is starting arguably the worst QB in the NFL.

Jacksonville Jaguars (-390)

Jacksonville had the best run defense in the NFL last year, holding opponents to 85.6 YPG. The Jags had a great pass defense, too, limiting teams to 218.1 passing YPG and forcing 31 total turnovers. 

The Jaguars also made the cut for my Week 1 NFL Survivor picks.

Cleveland is starting Deshaun Watson at quarterback in Week 1. Watson last played in 2024, when he went 1-6 as the Browns’ starter. He does have a 7-1 record against the Jaguars, but six of those wins came while Watson was with Houston.  

Bills vs. Texans

Texans super bowl odds
  • Verdict: Bet David Montgomery 64+ rushing yards
  • Best captured price: BetUS lists Montgomery at +118 for this prop
  • Break-even probability: 45.87%
  • Target price: -120 or shorter odds
  • Primary risk: Montgomery splits touches with Woody Marks.
  • Confidence: High – Buffalo allowed the 5th-most rushing yards last season.

David Montgomery 64+ Rushing Yards (+118)

Buffalo had the fifth-worst rushing defense in the NFL last year, allowing 136.2 rushing yards per game to opposing teams. Houston racked up 108 rushing yards against Buffalo last year, including 74 from their then-RB1 Woody Marks. Montgomery averaged 4.1 YPC for his career and will serve as the lead back for Houston against a poor Bills run defense.  

The Bills made major coaching changes this offseason, including hiring a new defensive coordinator, Jim Leonhard. However, Buffalo’s best DT, Ed Oliver, is recovering from an ankle injury, hurting Buffalo’s chances of stopping the run in Week 1.  

Cowboys vs. Giants

nfl best bets
  • Verdict: Bet on the Cowboys to win
  • Best captured price: BetUS lists Dallas at -160
  • Break-even probability: 61.54%
  • Target price: -250 or shorter
  • Primary risk: The Cowboys’ defense does not live up to expectations.
  • Confidence: High – Dak Prescott is 14-3 against the Giants in his career.

Dallas Cowboys (-160) 

Dallas opens the season on the road against a division rival, New York. Despite being the road team, the Cowboys are favorites in this divisional matchup. 

Dak Prescott is 14-3 against the Giants in his career, and two of those losses came during his rookie season. Dallas had one of the best offenses in the NFL last season, averaging the second-most YPG (391.4) and seventh-most PPG (27.7). 

Broncos vs. Chiefs

nfl week 11
  • Verdict: Bet on Broncos to cover
  • Best captured price: Lucky Rebel lists Denver at +2.5 (+100)
  • Break-even probability: 50%
  • Target price: +1.5-point spread or smaller
  • Primary risk: Bo Nix is recovering from multiple ankle surgeries this offseason.
  • Confidence: Moderate – Denver has a dominant defense and is 4-2 in its last six games against Kansas City.

Broncos +2.5 (+100) 

Denver is 4-2 in its last six regular-season matchups with the Chiefs, including a 20-13 win in Arrowhead last year. Also, the Chiefs have not beaten the Broncos by more than 2.5 points since 2023. 

The Broncos’ defense led the NFL in sacks last year with 68. Chiefs’ QB Patrick Mahomes is less than a year removed from major knee surgery to repair ACL and LCL tears. If Mahomes cannot scramble to get away from Denver’s pass rushers, then KC’s offense will be limited and struggle to cover the 2.5-point spread. 

The Market’s Best NFL Pick for Week 1

No team has better odds of winning in Week 1 than the Los Angeles Chargers. Lucky Rebel, BetUS, and BetOnline all list the Chargers as -550 home favorites against the lowly Arizona Cardinals. LA has an implied win probability of 84.62%.

The Chargers are -10.0 favorites at all three books, too. 

LA was a playoff team last year, has a franchise QB, and is led by one of the most respected coaches in football. Arizona, on the other hand, does not have a franchise QB and is led by an unproven rookie head coach, Mike LaFleur. 

The Lions are another heavy favorite who missed the cut for my list of top Week 1 picks. Detroit’s odds range from -320 (Lucky Rebel) to -305 (BetUS, BetOnline). They should win, but Detroit’s defensive issues from last season make them a risky bet to cover the 7.0 line against New Orleans.

Key Factors to Watch in NFL Week 1

  • 10 teams changed head coaches: Nearly a third of the league changed head coaches this offseason, so do not overly rely on stats from last season when making your predictions.  
  • Offenses usually start slow: Starting offenses have little to no playing time as a unit in the preseason, so expect some sloppy play in many Week 1 games. 
  • Lingering preseason injuries: Check for the latest injury updates before placing your bets to see which players may have lingering injuries that negatively affect their performance. 

What Are Your Week 1 NFL Predictions?

The Chargers (-550) have the best odds to win in Week 1, but I like the Jaguars (-390) payout odds better. Read the breakdown above to see my other Week 1 NFL predictions.

Check back every week for the latest NFL odds and my predictions throughout the season. 

(Photo from AP Photo/Asanka Brendon Ratnayake)

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About the Author

Shaun Stack, a native of the state of Kansas, has been a lifelong fan of all sports. Shaun has a Bachelor of Science in Psychology from the University of Pittsburgh Bradford. He has been writing for Gambling Nerd for several years, covering a wide range of topics.