Bills vs. Rams Prediction, Odds, Spread and Over/Under for NFL Week 1 (Don't Doubt Defending Champs as Home Dogs)

Los Angeles Rams head coach Sean McVay.
Los Angeles Rams head coach Sean McVay. / Mark J. Rebilas-USA TODAY Sports

Is there a better way to kick off the 2022 NFL season than the Buffalo Bills and Los Angeles Rams facing off on Thursday Night Football? 

NFL fans are in line for a fantastic matchup, as the defending Super Bowl Champion Rams take on the Super Bowl favorites in the 2022 season in Buffalo. Josh Allen and the Bills have an improved roster in 2022, although their defense will miss star cornerback Tre’Davious White, as he still recovers from a torn ACL. 

Matthew Stafford, Cooper Kupp and the Rams welcome Allen Robinson II into their dynamic offense as they look to make a statement win in Week 1 at home. 

How should we bet the first matchup of the NFL season? It starts with the odds from FanDuel Sportsbook: 

Bills vs. Rams Odds, Spread and Total 


  • Bills -2.5 (-106)
  • Rams +2.5 (-114)


  • Bills: -134
  • Rams: +114


  • 52.5 (Over -110/Under -110)

Rams vs. Bills Betting Trends

  • Sean McVay is 8-2 ATS in his career in Weeks 1 and 2
  • Defending Super Bowl Champions are 10-5-1 ATS in their weekday season opener over last 16 seasons
  • The Bills are 9-6 ATS as road favorites under Sean McDermott
  • The Rams are 1-3 ATS as home underdogs under Sean McVay
  • The OVER was 10-9 in Buffalo’s 19 games last season. 
  • The OVER was 10-10-1 in the Rams’ 21 games last season. 

Bills vs. Rams Prediction and Pick

There is always the fear of a Super Bowl hangover, but I don’t expect that from a team led by Sean McVay, especially against such a tough opponent. 

The Bills upgraded with Von Miller joining the team’s pass rush, but the loss of White could be huge in this game, as it could thrust rookie Kaiir Elam into a bigger role against Kupp and company. 

Remember, the last time we saw this Bills defense, it let the Kansas City Chiefs march into field goal range in just 13 seconds, eventually costing Buffalo a trip to the AFC title game. 

McVay has been fantastic to start seasons, and now he has one of the best rosters during his time in Los Angeles. I really am surprised that oddsmakers are so high on the Bills that Los Angeles is a dog in this game. 

I think the Rams actually can win this game straight up, especially if they can feed off the momentum from the per-game ring ceremony. 

LEAN: Rams ML (+114)

Find Peter Dewey’s full betting record here.