Los Angeles Chargers vs Buffalo Bills Picks and Prediction for Sunday September 27 2026

The Los Angeles Chargers visit the Buffalo Bills at Highmark Stadium in Orchard Park, New York, on Sunday, September 27, 2026. Kickoff is scheduled for 1:00 PM ET. Los Angeles enters at 0-2 after losing its first two games by identical 26-14 scores, including a home loss to Las Vegas in Week 2. Buffalo is 2-0 after beating Detroit 41-31 on Thursday night and has scored 77 points through its first two games. The Bills are currently favored by 7 points with a total of 50.5. Be sure to check out our free NFL picks for more NFL predictions throughout the season.

Los Angeles Faces a Difficult Road Test

The Chargers have been one of the more disappointing teams through the opening two weeks. Losing twice is concerning enough, but dropping both games by the exact same 26-14 score highlights an offense that has yet to find enough consistency. Los Angeles has scored only 28 points through two games and now has to travel across the country for an early-afternoon kickoff against one of the league’s hottest teams.

The Chargers cannot afford another slow offensive performance. Buffalo has already demonstrated that it can create separation quickly, and falling behind by multiple possessions would force Los Angeles into a game script that has not worked particularly well through two weeks. Sustaining drives and finishing red-zone opportunities with touchdowns instead of field goals will be critical.

The positive for Los Angeles is that Buffalo has not been impenetrable defensively. Detroit scored 31 points Thursday, so opportunities should exist if the Chargers can execute. Los Angeles does not necessarily need to hold Buffalo below 20 points to cover, but it probably needs its first offensive performance of the season that consistently produces points.

Buffalo’s Offense Has Set the Early Pace

Buffalo could hardly have started better offensively. The Bills are 2-0 and have scored 77 points, including 41 in their Week 2 victory over Detroit. They also receive extra preparation time after playing Thursday, while Los Angeles must make a cross-country trip following Sunday’s loss.

The biggest matchup advantage is Buffalo’s ability to create scoreboard pressure. Los Angeles has reached only 14 points in each of its first two games. If Buffalo pushes into the upper 20s or low 30s again, the Chargers would have to dramatically exceed their early-season offensive production simply to remain within the spread.

There is some danger in laying a full touchdown against an opponent capable of improving offensively, especially after Buffalo surrendered 31 last week. Still, the Bills have established a substantially higher offensive ceiling through two games and have home field plus a rest advantage. That combination makes Buffalo difficult to oppose.

Los Angeles Chargers vs Buffalo Bills Picks and Prediction

Pick: Buffalo Bills -7

Buffalo -7 is the side pick. The Bills have scored 77 points during their 2-0 start, while Los Angeles has produced only 28 during an 0-2 start. Buffalo also has extra rest and home-field advantage against a Chargers team making a long trip east. Los Angeles may eventually find its offensive rhythm, but this is a difficult matchup in which to expect that turnaround.

Pick: Under 50.5

The Under 50.5 is the total pick. Buffalo is certainly capable of doing its share, but Los Angeles has scored exactly 14 points in each game. The Chargers would likely need to approach the mid-20s for this total to become uncomfortable unless Buffalo produces another 40-point performance. A result around 30-17 or 31-17 gives the Bills enough offense to cover while remaining below the number.

Final Picks: Buffalo Bills -7 and Under 50.5