LAC vs BUF Prediction, Odds and NFL Picks for Sunday, 09/27/26

We have a matchup between a couple of AFC teams trending in different directions on Sunday, as the Buffalo Bills will host the Los Angeles Chargers in a game that could end up deciding the season for the visitors. Few teams have looked worse through the first two weeks than the Chargers, while the Bills are off to a fantastic start in the Joe Brady era. Spirits are high in Buffalo after an impressive first few weeks, and the market has clearly adjusted accordingly. The Bills are either already overvalued at this point, or a team that is only going to keep ascending as the season goes along. While I would ordinarily look to fade the early season hype in Buffalo at this stage, I can't possibly back Los Angeles in this spot.

There are so many things wrong with this Chargers team that it's hard to even find where to start. Justin Herbert has been miserable through two weeks, and it makes sense considering the injuries on the offensive line, wide receiver and tight end that his team is dealing with. The Mike McDaniel offense is clearly not working with the personnel that he has on an offense that doesn't have much talent. On the other side of the ball, the Los Angeles defense has been extremely weak without Jesse Minter on the sidelines calling plays, and that doesn't even account for some key injuries in the secondary that it has to deal with this week. Throw in a cross-country road trip and a meeting against the top offense in the NFL at the moment, and I'd need closer to double digits to back the Chargers in this one.

Chargers vs Bills prediction: Bills -7 available at time of publishing. Playable at that number or better.

Regardless of which team covers the spread, the under is my preferred look on the total in this game. It's hard to find much to like with this Chargers offense at the moment. Justin Herbert has been terrible, the offensive line has committed the most penalties in football and there's just no rhythm on the ground or through the air over the first two weeks. That could change against a suspect Bills secondary, but one thing Buffalo has is a pass rush — which could make life miserable for Herbert in a difficult road environment.

On the other side, the Bills have been extremely explosive thus far, but Buffalo could settle into a more run-heavy game script once they get a lead. These possessions could chew up clock and shorten the game a bit as well. All things considered, I'll back the under in Buffalo.

Chargers vs Bills prediction: Under 50.5 (-110) available at time of publishing. Playable to 50.