The Los Angeles Rams will face the NFL's toughest schedule based on opponent winning percentage this season, which could make it difficult to make another Super Bowl run this year. Their grueling schedule begins with a matchup against the Buffalo Bills in the 2022 NFL Kickoff Game on Thursday. Buffalo is the preseason 2023 Super Bowl favorite at Caesars Sportsbook and returns talent include quarterback Josh Allen, wide receiver Stefon Diggs, and running back Devin Singletary. The Rams counter with quarterback Matthew Stafford, record-setting wide receiver Cooper Kupp, and running back Cam Akers.

Kickoff from SoFi Stadium is set for 8:20 p.m. ET. Buffalo is a 2.5-point favorite in the latest Bills vs. Rams odds from Caesars Sportsbook, while the over/under for total points scored is 52. Before making any Rams vs. Bills picks, make sure to check out the expert NFL predictions and betting advice from SportsLine's proven computer model

The model, which simulates every NFL game 10,000 times, is up over $7,500 for $100 players on top-rated NFL picks since its inception. The model enters the 2022 NFL season on an incredible 138-97 run on top-rated NFL picks that dates back to the 2017 season. Amazingly, it hasn't missed a top-rated pick since Week 15 last season.

The model also ranked in the top 10 on NFLPickWatch four of the past six years on straight-up NFL picks and beat more than 94 percent of CBS Sports Football Pick'em players four times during that span. Anyone who has followed it is way up.

Now, the model has simulated Bills vs. Rams in the NFL Kickoff Game 2022 10,000 times and just revealed its NFL expert picks and predictions. You can head to SportsLine now to see its picks. Here are several NFL odds and betting trends for Rams vs. Bills:

  • Bills vs. Rams spread: Buffalo -2.5
  • Bills vs. Rams over/under: 52 points
  • Bills vs. Rams money line: Buffalo -135, Los Angeles +115
  • BUF: Bills scored at least 31 points in 11 of their 19 games last season, including playoffs
  • LAR: Rams have lost their last three home games against Buffalo
  • Bills vs. Rams picks: See picks at SportsLine
Featured Game | Los Angeles Rams vs. Buffalo Bills

Why the Bills can cover

Buffalo owns an 8-5 record in the all-time series against the Rams and has won seven of the last nine matchups. It has captured its last three road meetings, including a 30-19 triumph at Los Angeles in 2016, and posted a 35-32 home victory in the most recent encounter two seasons ago. Josh Allen put on a show in that contest, running for a touchdown while throwing his fourth scoring pass of the game with 15 seconds remaining in the fourth quarter.

One of Allen's TD tosses in that triumph went to Stefon Diggs, who has been the quarterback's top target since being acquired from Minnesota in March 2020. The 28-year-old wideout from the University of Maryland led the NFL while setting career-highs in catches (127) and receiving yards (1,535) in his first year with the Bills and hauled in 164 passes for 1,225 yards last season. Diggs, who is third in the league in receptions over the last two years, needs 105 in 2022 to become the sixth player in NFL history with 700 in his first eight campaigns.

Why the Rams can cover

One of Buffalo's weaknesses is on the offensive line, which does not bode well against one of the best defensive fronts in the NFL. The Rams did not allow more than 100 rushing yards in 13 games last season, going 11-2 in those contests. Buffalo went winless in four games when rushing for fewer than 100 yards in 2021-22, so that is a telling stat that favors the Rams on Thursday.

The defending champions are led by veteran quarterback Matthew Stafford, who will try not to let his team suffer from a Super Bowl hangover. Los Angeles won nine of its final 10 games last season and has covered the spread in five consecutive season-openers. The Rams are 13-2 in their last 15 September games.

How to make Rams vs. Bills picks

SportsLine's model is leaning Under on the total, projecting the teams to combine for 49 points. It also says one side of the spread cashes in well over 50% of simulations. Head to SportsLine to see its NFL picks

So who wins Bills vs. Rams in the NFL Kickoff Game 2022? And which side of the spread cashes well over 50% of the time? Visit SportsLine now to see the Bills vs. Rams picks, all from the model that has returned over $7,500 on top-rated NFL picks, and find out.