The Los Angeles Chargers enters Sunday afternoon's 1 p.m. ET matchup as sizable +7.5 underdogs against the Buffalo Bills at Highmark Stadium, and my Chargers vs. Bills prediction expects the visitors to stay within the number.
Find out more in my NFL picks for Sept. 27 below.
TOP Pick
Chargers vs Bills prediction: Chargers +7.5
Take the points with the Los Angeles Chargers to 54%, as the spread sits above the key number of 7.
The Bolts are in a desperation spot, and the Buffalo Bills haven’t shown off on defense with the fifth-highest EPA per play allowed while ranking 19th in defensive DVOA.
Additionally, the Chargers have allowed the seventh-lowest EPA per rush, and the Bills have a banged-up receiving corps with both D.J. Moore (shoulder) and Keon Coleman (ankle) practicing sparingly this week.
It all adds up to Bolts sustaining drives to keep this game competitive, or Los Angeles coming through late with the backdoor cover against a leaky Buffalo defense on Sunday afternoon.
COVERS INTEL: The Buffalo Bills have allowed the third-highest passer rating, so with Los Angeles Chargers quarterback Justin Herbert’s 71.9 mark way below his career 96.3 passer rating entering the season, he’s set up for a rebound showing in Week 3.
Chargers vs Bills combo
The Bills grade 23rd in PFF run defense, and I’m expecting the Bolts to lean on running back Omarion Hampton early and often in an attempt to keep the clock churning and Bills superstar Josh Allen watching from the sideline.
Hampton has also rushed for 3.2 yards after contact per attempt with a high-end 103.8 PFF Elusive Rating while handling 66% of the team’s carries.
The go-to rusher has scored in consecutive games, too, and Buffalo has surrendered four touchdowns to opposing running backs already.
Chargers vs Bills combo
- Chargers +7.5
- Omarion Hampton 60+ rushing yards
- Omarion Hampton anytime touchdown
Chargers vs Bills touchdown scorer: Omarion Hampton
Building on the case for Hampton to find the end zone, he has handled 50% of the touches in the red zone for the Bolts and has converted both his rushes inside the 10-yard line into touchdowns.
Additionally, Buffalo has allowed opponents to score touchdowns on seven of their nine trips to the red zone for the eighth-highest 77.8% rate.
Chargers vs Bills player prop: Ladd McConkey 55+ receiving yards
With the Bills allowing the fifth-highest EPA per dropback in the second half, Chargers wide receiver Ladd McConkey has my attention. He’s been a full participant in practice all week and has a solid 14.6 yards per reception and 13.8 aDoT through two games.
McConkey has also garnered a high-end 23.9% of the team’s air yards with an 18.9% target share. Plus, Buffalo has surrendered the ninth-highest yards per target (9.16) to opposing wideouts through two weeks.
Want more NFL player props? Check out our NFL player prop projections!
- Top picks: 13-10, +2.25 units
- Combos: 0-5, -5.0 units
Chargers vs Bills odds
For help understanding probabilities, see our odds calculator.
- Spread: Chargers +7.5 | Bills -7.5
- Over/Under: Over 50.5 (48%) | Under 50.5 (53%)
- Moneyline: Chargers 25% | Bills 75%
For the full slate of NFL matchups, check out our NFL odds board!
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Chargers vs Bills weather
The forecast calls for temperatures topping out at 64°F, accompanied by steady northeast winds blowing around 11 to 13 mph with gusts up to 20 mph.
Orchard Park is expected to be cloud-covered with potential light showers during Sunday's game.
Check out our NFL weather page for up-to-date info on every matchup.
Chargers vs Bills trend to know
The Los Angeles Chargers have only won nine of their last 20 games (-10.70 Units / -26% ROI). Find more NFL betting trends for Chargers vs. Bills.
How to watch Chargers vs Bills
| Location | Highmark Stadium, Orchard Park, N.Y. |
| Date | Sunday, Sept. 27, 2026 |
| Kickoff | 1 p.m. ET |
| TV | FOX |
Chargers vs Bills latest injuries
Check out our NFL injuries page for updates on every team.
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