Best NFL Picks and Predictions Today (How to Bet Bills vs. Rams on Monday Night Football in NFL Week 5)

Can you say, “Super Bowl preview?”

That’s what we may have on our hands in Week 5 of the 2026 NFL season, as the Buffalo Bills hit the road to play the Los Angeles Rams on Monday night. Both of these teams are inner circle contenders to win the Super Bowl, and they entered Week 5 as the No. 1 (L.A.) and No. 2 (Buffalo) teams in the latest Super Bowl odds.

Josh Allen and the Bills are looking to bounce back from a home loss to the New England Patriots, but they are set as underdogs in this Week 5 matchup. The Rams have been the No. 1 team in the power ratings for various sportsbooks that have spoken to Sports Illustrated and they’ve remained in that spot despite some injuries (mainly to Myles Garrett) and a 2-2 start.

L.A. avoided a 1-3 start with a huge fourth-quarter comeback against the Philadelphia Eagles in Week 4, and it’s hoping to avoid a double-digit fourth quarter deficit in Week 5.

There are plenty of interesting storylines to watch in this game, which features a Rams defense that was third in the NFL in EPA/Play through four weeks taking on a Buffalo offense that has been a top-10 unit in success rate and EPA/Play.

So, who has the edge in primetime?

In the lead up to this marquee matchup, the SI Betting team has made game picks, player prop selections and much more to get our readers ready for Bills vs. Rams.

I’ve compiled a bunch of our favorite plays to make this a one-stop shop for Monday night’s showdown.

Best NFL Picks and Predictions for Bills vs. Rams

Odds via DraftKings Sportsbook

Los Angeles Rams -3 (-110) vs. Buffalo Bills – Iain MacMillan
Josh Allen Anytime TD (-115) – Peter Dewey
Davante Adams OVER 64.5 Receiving Yards (-115) – Iain MacMillan
James Cook OVER 75.5 Rushing Yards (-111) – Peter Dewey

Los Angeles Rams -3 (-110) vs. Buffalo Bills – Iain MacMillan

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.

Josh Allen Anytime TD (-115) – Peter Dewey

Josh Allen has found the end zone in every game so far this season, yet he’s only -115 to score in a game where several players are set at minus odds to hit paydirt.

Allen’s rushing did come down in Week 4 – he only had five carries for four yards and a score – but he’s scored seven total touchdowns in 2026 and remains one of the best goal-line options in the league.

Even with his rushing usage decreasing in Week 4, Allen still has 33 carries this season and at least five in every game. That gives him a pretty solid floor when it comes to this prop, and he’s scored 12 or more rushing touchdowns in each of his last three completed seasons.

Davante Adams OVER 64.5 Receiving Yards (-115) – Iain MacMillan

This week, MacMillan shared his top 10 props for Week 5 in his Player Prop Countdown, and he has this play for Davante Adams at No. 3:

Not enough people are talking about how bad the Buffalo Bills' secondary has been.

They're 27th in both opponent dropback EPA and opponent dropback success rate. With that in mind, I'll target Davante Adams to go over his receiving yards total.

It's 30 yards lower than Puka Nacua's, but I still have some concerns about Nacua being fully healthy in this game.

James Cook OVER 75.5 Rushing Yards (-111) – Peter Dewey

James Cook has been a little underutilized at times in this Buffalo offense, especially since he's been so effective in 2026.

The reigning rushing yards leader is averaging 6.0 yards per carry this season, finishing with 75 yards on just 12 carries in Week 4. He’s cleared 130 rushing yards in both games where he saw over 20 carries.

The Bills would be smart to involve Cook more, especially since the Rams defense has been beatable on the ground (14th in EPA/Rush). L.A. is third in EPA/Pass this season.

Cook should reach this line as long as Joe Brady is willing to give his star running back a major workload, as he’s fallen short of it in Weeks 1 and 4 when he saw less than 15 carries.

I’m betting on a bounce-back game for the star back in primetime.

Odds refresh periodically and are subject to change.

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