The Buffalo Bills are looking to hand the Los Angeles Chargers an 0-3 start as huge home favorites ahead of their 1 p.m. ET kickoff at Highmark Stadium on Sunday, Sept. 27.
My early Chargers vs. Bills prediction and NFL picks are calling for Buffalo to cover the number while holding the Los Angeles offense in check in Week 3.
Chargers vs Bills predictions
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Early Chargers vs Bills spread pick: Bills -6.5
I haven’t seen any spark in the Los Angeles Chargers through two weeks, while the Buffalo Bills have pummeled their way to a 2-0 start with statement victories over quality teams.
While the Bills definitely have questions to answer on defense, superstar Josh Allen has shown off while throwing for 9.7 yards per attempt with the third-highest EPA per play ahead of Monday Night Football in Week 2.
By comparison, Los Angeles QB Justin Herbert ranks 28th in EPA per play.
Additionally, the Chargers have scored a touchdown on just 7.7% of their possessions, while the Bills have found the end zone in a league-high 15.9% of their series.
This spread is giving too much credit to a crumbling Chargers season.
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Early Chargers vs Bills total pick: Under 49.5
The Bills have the third-highest pressure rate and rank third in PFF pass rush grade, so Herbert and the 0-2 Chargers will be even more up against it heading east to the hostile Highmark Stadium environment.
With the Chargers checking in 30th in PFF offense grade and 28th in offensive success rate, I expect Buffalo to hold Los Angeles in check enough to keep this total Under the number.
Of course, this is also a must-win game for Los Angeles, and I do expect a top effort from the stop unit. The Chargers have been stingy against the run and allowed the eighth-lowest EPA per rush and sixth-lowest rush success rate, so there has been a pulse on that side of the ball.
Finally, from a game-plan perspective, I anticipate Chargers head coach Jim Harbaugh will be looking to avoid a high-scoring shootout at all costs Sunday.
Chargers vs Bills odds
For help understanding Kalshi probabilities, see our odds calculator.
- Chargers vs Bills spread: Bills -6.5
- Chargers vs Bills moneyline: Chargers 26%, Bills 75%
- Chargers vs Bills Over/Under: 49.5
How to watch Chargers vs Bills
- Date: Sunday, Sept. 27, 2026, 1 p.m. ET
- City: Orchard Park, NY
- Venue: Highmark Stadium
- TV: FOX
Odds are correct at the time of publishing and are subject to change.
Not intended for use in MA.
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