Bills vs. Rams Score Prediction for NFL Week 5 (Bet on Los Angeles at Home?)

Week 5 of the 2026 NFL season closes out with a potential Super Bowl preview, as the Los Angeles Rams and reigning league MVP Matthew Stafford take on the Buffalo Bills and current MVP favorite Josh Allen on Monday night.

These two teams entered Week 5 as the top squads in the odds to win the Super Bowl, and they’re about as closely rated as two teams could be.

“For this particular game, on a neutral field, it would probably be priced as a pick 'em,”Ty Gour, Sports Trader at Fanatics Sportsbook, told Sports Illustrated. “And the reason for that being no Myles Garrett and possibly no Aaron Donald as well, that's just going to take a little bit away from the Rams' defense. However, fully healthy on a neutral field, and that includes Josh Allen as well, the Rams probably land about a 1- to 1.5-point favorite. We don't see much of a gap right now between the two teams, but still notable enough for us to declare the Rams as No. 1.”

The Rams are favored by a little more at home in this Week 5 clash, they’re coming off an impressive comeback win over the Philadelphia Eagles in Week 4. L.A. trailed by 10 points in the fourth quarter, but two late touchdown drives helped it avoid a shaky 1-3 start. Still, the Rams are in danger of falling back under .500 against Allen and an elite Buffalo offense.

The Bills didn’t do themselves any favors in Week 4, losing at home against their division rival – the New England Patriots. In back-to-back weeks, the Buffalo offense has looked shaky, and Allen (knee) didn’t run the ball much in Week 4. Does that change in a crucial road matchup in primetime?

All season long, the SI Betting team is predicting the final score of just about every NFL game, a fun exercise to help bettors decide on their spread, moneyline and total bets. I’m looking to nail this score for the matchup of the week between Buffalo and Los Angeles.

Here’s a breakdown of my score prediction, as the NFL closes out Week 5 with a banger on Monday night.

Bills vs. Rams Odds, Spread and Total

Odds via DraftKings Sportsbook

Spread

Bills +3 (-115)
Rams -3 (-105)

Moneyline

Bills: +136
Rams: -162

Total

54.5 (Over -118/Under -102)

Both the spread and total have shifted in this game after opening with the Rams as 2.5-point favorites and the total at 53.5. Oddsmakers are clearly expecting a high-scoring affair between these two teams, but the Rams are No. 3 in EPA/Play on defense so far in the 2026 campaign.

Bills vs. Rams Score Prediction

This week – and all season long – SI Betting’s Iain MacMillan shares his favorite bet for every game in his Road to 272 column. On Monday night, he’s taking the Rams to take care of business at home:

It's not being talked about enough how bad the Bills' defense has been this season. It led to them losing in Week 4 to the Patriots, and now they have to face the reigning MVP and Puka Nacua, who's going to start hitting his stride. Buffalo now ranks 30th in opponent EPA per play and 28th in opponent success rate. The only defenses that have been worse are the Lions' and Cowboys'.

Meanwhile, the Rams defense is third in opponent EPA per play and fifth in opponent success rate. They're also a top-10 defense in stopping the run, a huge key in slowing down the Bills' offense.

If Buffalo can't rack up the points in this game, the Rams are going to leave them in the dust against this defense. I'm not afraid to lay the points on Los Angeles.

After two weeks of dominance, the Buffalo offense has really come back to earth the last two weeks with Allen turning the ball over multiple times. Now, the Bills are down to 10th in the NFL in offensive success rate, and they’re taking on a Rams defense that has proven to be one of the best in the league (as MacMillan mentioned) even with Myles Garrett out.

The Bills beat up on a Houston team that started the season 0-4 and a Detroit defense that can’t stop anyone this season in the first two weeks, and I’m not sure it is on the same level as a Rams team that has already had to play San Francisco, Denver and Philadelphia to open the season.

I’ll lay the points with the Rams in what should be an instant classic.

Final Score Prediction: Rams 27, Bills 24

Odds refresh periodically and are subject to change.

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