6 Matchups That Will Decide Chargers' Week 3 Game Against the Buffalo Bills

The Chargers will look to slow down the dangerous Buffalo Bills. See some of the key matchups that will dictate the outcome of this game.

Dec 23, 2023; Inglewood, California, USA; Buffalo Bills quarterback Josh Allen (17) throws a pass during the third quarter against the Los Angeles Chargers at SoFi Stadium. Mandatory Credit: Kiyoshi Mio-USA TODAY Sports | USA TODAY Sports via Reuters Connect

The Los Angeles Chargers will head to Buffalo to try to slow down Josh Allen and the surging Buffalo Bills. Los Angeles is dealing with significant injuries on top of their 0-2 start to the 2026 season.

There are several key matchups that will dictate whether the Chargers have a shot in taking down the Bills this week. Let's go through some of the biggest matchups of the week.

Akheem Mesidor vs. Josh Allen

Sep 20, 2026; Inglewood, California, USA; Los Angeles Chargers edge rusher Akheem Mesidor (90) brings down Las Vegas Raiders quarterback Kirk Cousins (8) during the first half at SoFi Stadium. Mandatory Credit: Kirby Lee-Imagn Images | IMAGN IMAGES via Reuters Connect

Why would a rookie edge rusher against arguably the best quarterback in the NFL be a key matchup? It is simple, one of Josh Allen's best and most dangerous traits is his ability to run and scramble. Khalil Mack and Tuli Tuipulotu may not be fast enough to track down or keep up with Allen is he has a runway to the outside.

Akheem Mesidor is big enough and fast enough to track down Allen and has the burst to close. The Chargers edge rushers will look to stay disciplined and stick to their rush lanes to contain Allen in the pocket, but if he escapes, Mesidor may be the x-factor in stopping an Allen explosive run or two.

Chargers tackles vs. Bills edge rushers

Dec 19, 2024; Inglewood, California, USA; Los Angeles Chargers quarterback Justin Herbert (10) drops back to pass as offensive tackle Rashawn Slater (70) blocks against Denver Broncos linebacker Nik Bonitto (15) during the second half at SoFi Stadium. Mandatory Credit: Gary A. Vasquez-Imagn Images | USA TODAY Sports via Reuters Connect

Bills edge rushers Gregory Rousseau and Bradley Chubb have been successful getting to opposing quarterbacks. The pair already have notched six sacks on the season and will be a big challenge for Rashawn Slater and Joe Alt.

Deone Walker vs. Chargers interior offensive line

Aug 23, 2025; Tampa, Florida, USA; Buffalo Bills defensive tackle Deone Walker (96) reacts after a play against the Tampa Bay Buccaneers in the first quarter at Raymond James Stadium. Mandatory Credit: Nathan Ray Seebeck-Imagn Images | IMAGN IMAGES via Reuters Connect

I jokingly nicknamed Deone Walker the boogeyman as a draft prospect. He is enormous with quick feet and the ability to fly through the line of scrimmage. Even if Ed Oliver is unable to play, the Chargers interior offensive line will have their hands full with Walker.

Ladd McConkey vs. Dee Alford

Sep 20, 2026; Inglewood, California, USA; Los Angeles Chargers wide receiver Ladd McConkey (15) celebrates after a play against the Las Vegas Raiders during the first half at SoFi Stadium. Mandatory Credit: Kirby Lee-Imagn Images | IMAGN IMAGES via Reuters Connect

Ladd McConkey has been the Chargers best and only consistent wide receiver so far this season. If he aligns in the slot, the Bills deploy Dee Alford as their slot cornerback. Alford has been prone to giving up catches and yards. McConkey against Alford will be a big factor in the Chargers passing game.

Chargers linebackers vs. James Cook

Buffalo Bills running back James Cook has a large space to run and almost makes it to the end zone before getting tackled during the second half at the Bills home opener game against the Detroit Lions on Sept. 17, 2026. | USA TODAY Network via Reuters Connect

Bills running back James Cook is currently averaging 5.6 yards per attempt on the ground and has excellent vision. The Chargers linebackers will have to be disciplined in their run fits and close rushing lanes quickly.

Chargers linebackers and defensive backs vs. Dalton Kincaid

Sep 20, 2026; Inglewood, California, USA; Los Angeles Chargers safety Tony Jefferson (23) is introduced prior to the game against the Las Vegas Raiders at SoFi Stadium. Mandatory Credit: Gary A. Vasquez-Imagn Images | IMAGN IMAGES via Reuters Connect

Bills tight end Dalton Kincaid presents a problem for every defense. Kincaid is averaging nearly 19 yards per reception and 112 yards per game through the first two weeks. The Chargers linebackers have to contend with Josh Allen's ability to run and Kincaid getting behind them and he lines up 50 percent of the time as the inline tight end. Whichever defensive backs tasked with covering him need to be prepared to tackle him though, he is averaging 6.5 yards after the catch with an average depth of target just shy of 13 yards indicating he is doing his damage deep into the secondary.