Chargers vs. Bills Score Prediction for NFL Week 3 (Don’t Trust L.A. Against Buffalo Offense)

Josh Allen and the Buffalo Bills are off to a 2-0 start this season, ranking No. 1 in EPA/Play on offense by scoring 77 points in their first two games. As a result, Allen is the clear favorite to win the MVP in 2026.

In Week 3, the Bills host the Los Angeles Chargers and Justin Herbert, who have lost back-to-back games as major favorites against Arizona and Las Vegas. That has tanked the Chargers’ playoff odds, as those two games were considered some of the easiest on the team’s schedule.

Now, L.A. is a seven-point underdog in Week 3 against the Bills, and it’s facing an uphill battle just to cover with such a high-powered offense. Buffalo’s defense has struggled to open this season, but 10 days off between games (the Bills played on Thursday in Week 2) should help Ed Oliver and others return to the lineup on that side of the ball.

A win for the Bills would be huge in the race for the No. 1 seed, and a loss could put an early end on the Chargers’ playoff chances. So, how should we bet on this Week 3 matchup?

All season long, the SI Betting team is sharing score predictions for just about every NFL matchup. Not only will we predict every score for Sunday’s games, but we will also have several individual score prediction stories to help bettors make their spread, moneyline and total picks.

The goal? We’re using the latest odds, market movement and picks from our team to guide bettors in the right direction for their NFL plays, and potentially get a score exactly correct in the process.

Now, let’s dive into the score prediction for what has become a must-win game for L.A.

Chargers vs. Bills Odds, Spread and Total

Odds via DraftKings Sportsbook

Spread

Chargers +7 (-105)
Bills -7 (-115)

Moneyline

Chargers: +275
Bills: -345

Total

50.5 (Over -105/Under -115)

This line has held steady since opening with the Bills as seven-point favorites, which shows just how far the sentiment around the Chargers has fallen since before the start of the season.

Chargers vs. Bills Score Prediction

This week, SI Betting’s senior editor Iain MacMillan made a pick for this game in his Road to 272 column, where he bets on every game, every week. He’s taking the OVER rather than a side in this AFC clash:

The Los Angeles Chargers take the award as the most surprising team through the first two weeks, which puts us in a tough spot as bettors. Do we change our evaluation of them and start rating them as a bottom-10 team in the NFL, or do we buy low and expect them to turn things around?

Instead of making a call one way or another on that decision, I'm going to forego betting on the spread and focus on betting the total instead.

The Bills' offense has been unbelievable, but their 2-0 record has allowed people to overlook how bad their defense has been. They have given up 5.5 yards per play, and they rank 27th in both opponent EPA per play and opponent success rate.

The Chargers' offense has a great chance to bounce back here. I can't imagine Herbert's struggles will continue, so I'm going to bet on this being a high-scoring affair.

While I don’t disagree with MacMillan’s OVER bet, there is a glaring issue that I can’t get past.

Buffalo is No. 1 in the NFL in EPA/Play on offense by a wide margin while the Chargers clock in at No. 30. As much as I want to believe that Herbert can turn things around, the Chargers just choked away two games against far worse teams – on their home field!

Buffalo may need to outscore the Chargers to win, but Joe Brady’s group has shown no problems doing that, dismantling a strong Houston defense before dropping 41 points on a leaky Detroit secondary on Thursday night.

The Bills and Allen have a major rest advantage in this game, and they’ve shown they have the best unit (their offense) in this matchup. I’ll lay the points with the Bills in what could be a barnburner on Sunday.

Final Score Prediction: Bills 34, Chargers 23

Odds refresh periodically and are subject to change.

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