With the Bills laying between 2 and 2.5 points on oddsboards, Buffalo’s trip to LA to meet the Rams marks the first time in six years a defending NFL champion is a home underdog in the NFL season opener. Denver was a 3.5-point dog against Carolina in 2016 and prevailed 21-20. The past 20 years, the defending Super champs are 13-5-3 ATS in Week 1.
The Rams were betting underdogs twice last season and won both games outright, at Arizona (30-23, +3.5) and in the divisional playoff round at Tampa Bay (30-27, +2.5). They haven’t been a home dog since 2020 in the first regular-season game ever played at SoFi Stadium, beating Dallas 20-17 at +2.
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Bills vs. Rams Betting Lines: TNF Points Spread, Moneyline, Total
Here are odds from around the sports betting marketplace on the 2022 NFL Season Kickoff Game
NFL · Thu (9/8) @ 8:22pm ET
BUF Bills | at | LA Rams |
SoFi Stadium, Inglewood, California |
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Rams Face Tough Bills D
Buffalo, which had the league’s top-ranked defense last year, gave five foes their most lopsided defeat, including a 47-17 victory over New England in the wild-card round. LA had three such games.
The Rams had only the 17th-ranked defense in 2021, a season after being No. 1, but ranked third in sacks (50) and held three opponents to less than 200 yards in a game, a league-high. Two of those games came after the acquisition of eight-time Pro Bowl LB Von Miller from Denver. He’s now with the Bills.

Buffalo was particularly sharp in pass defense last season, holding three teams’ QBs to fewer than three yards per drop-back. All other clubs totaled eight such efforts.
A key absence in this game is star Bills cornerback Tre’Davious White (knee), who’s on the reserve/PUP list. Getting a start at CB will be rookie first-round pick Elam Kaiir out of Florida. Also, LB Matt Milano is rated as one of the best at his position in pass coverage
That secondary will have to contend with the pass-catch tandem of QB Matt Stafford and WR Cooper Kupp (+6000 to win league MVP, DraftKings), who won the NFL’s receiving triple crown last year (catches, yards, TDs). Maybe make it a quadruple crown since he was tops in yards after the catch, too. Stafford, though, tied for the most INTs last season with 17, including a league-high four pick-6s.
Also read: NFL Week 1 Picks | NFL Week 1 Teaser Picks | Week 1 NFL Power Rankings
Bills vs. Rams Betting Analysis & Prediction
If a team has to endure a coast-to-coast travel week now’s the time to do it.
Buffalo was strong all last season in setting the pace in the AFC East, but picked up even more steam deep into the season, with QB Josh Allen throwing for nine TDs and no INTs in his two playoff games and with RB Devin Singletary also excelling, getting six rushing TDs his final four games. He’ll no doubt share the running load with speedy rookie James Cook, a second-round pick out of Georgia.
And, of course, WR Stefon Diggs, who had 103 catches last season, is back.
But it won’t be easy for the Bills, who will have to contend with seven-time All-Pro DT Aaron Donald and standout LB Bobby Wagner, a former leader for Seattle’s Legion of Boom. Buffalo’s offensive line could have issues handling that pair.
But it could be even harder for the Rams despite the return of RB Cam Akers from his Achilles issues last year and the addition of WR Allen Robinson, who had an off-year in Chicago in 2021. The retirement of OLT Andrew Whitworth, a four-time Pro Bowler, won’t be easy to overcome.
And, finally, what are the chances the Bills’ new pass-rush terror, Miller, just might have some inside information on Stafford’s tendencies?
Forecast: Bills 27, Rams 20
Also check: NFL Week 1 odds | Super Bowl 57 odds