Los Angeles Chargers vs Buffalo Bills Prediction 9/27/2026 Today’s NFL Picks
Chris Ruffolo
Bills Josh Allen runs towards the sidelines and extra yards during the second half at the Bills home opener game against the Detroit Lions on Sept. 17, 2026.
MATCHUP
Los Angeles Chargers
Buffalo Bills
Team Records
0-2
2-0
Spread
+7 -105
-7 -115
Moneyline
+275
-345
Total
Over 50.5 (-102)
Under 50.5 (-118)
Where
Highmark Stadium, Orchard Park, NY
When
Sunday, September 27, 2026
Time
01:00 PM EDT
TV
FOX
The Los Angeles Chargers and the Buffalo Bills meet in week 3 NFL action from Highmark Stadium on Sunday. We will look at this from a betting perspective and determine the best bets for this game. Here’s a Los Angeles Chargers vs. Buffalo Bills prediction.
Los Angeles Chargers Recap
The Los Angeles Chargers come into this game looking to bounce back from a 26-14 loss at the hands of Las Vegas last time out to sit at 0-2 this season. After this game, the Chargers will head on the road for a game against Seattle.
Chargers Looking For First Win
Justin Herbert has thrown for 401 yards, 2 touchdowns and 3 interceptions on 59.3% passing while Omarion Hampton leads Los Angeles in rushing with 137 rushing yards and 2 touchdowns so far this season. Keaton Mitchell sits behind Hampton on the ground with 33 yards and 0 TDs. Ladd McConkey leads the Chargers in receiving with 117 yards on 8 catches along with 1 touchdown, while Tre’ Harris trails with 73 yards on 4 catches along with 1 touchdown. On defense, Derwin James Jr. has a team-high 17 total tackles, Khalil Mack leads the unit with 1 sack, and Cam Hart recorded the team’s lone interception. Los Angeles’s defense as a whole has combined for 3 sacks and 1 interception so far this season.
Buffalo Bills Recap
The Buffalo Bills come into this game looking to add on to their 41-31 win over Detroit last time out to sit at 2-0 this season. After this game, the Bills will head home for a game against the New England Patriots.
Bills Looking To Stay Unbeaten At Home
Josh Allen has thrown for 582 yards, 5 touchdowns and 0 interceptions on 66.7% passing while James Cook III leads Buffalo in rushing with 192 rushing yards and 1 touchdown so far this season. Josh Allen sits behind Cook III on the ground with 92 yards and 4 TDs. Dalton Kincaid leads the Bills in receiving with 225 yards on 12 catches along with 1 touchdown, while DJ Moore trails with 100 yards on 5 catches along with 1 touchdown. On defense, Terrel Bernard has a team-high 17 total tackles, while Greg Rousseau leads the unit with 4 sacks. Buffalo’s defense as a whole has combined for 7 sacks and 0 interceptions so far this season.
Los Angeles Chargers @ Buffalo Bills Betting Trends: Week 3
Why the Buffalo Bills will win
The Bills have won each of their last 17 home games against opponents on a losing streak.
The Chargers have lost each of their last nine games as underdogs against opponents on a winning streak.
The Chargers have failed to cover the spread in each of their last six games as road underdogs against AFC East opponents.
The Bills have covered the spread in each of their last four games when playing with a rest advantage.
The Chargers have lost the first quarter in five of their last six road games against AFC opponents.
The Bills have scored the first touchdown in 10 of their last 11 Week 3 games.
The Chargers have lost the first half in each of their last six games as road underdogs against AFC East opponents.
Why the Los Angeles Chargers will win
The Chargers have won each of their six previous September games against the Bills.
The Bills have lost three of their last four games as favorites following a home win.
The Bills have failed to cover the spread in five of their last six games without Dawson Knox.
The Chargers have covered the spread in five of their last six road openers.
The Chargers have won the first quarter in seven of their last eight September games as underdogs.
The Chargers have scored the first touchdown in six of their last seven Week 3 games.
The Chargers have won the first half in each of their last eight September games as underdogs.
Total Points Facts
Each of the Bills’ last nine home games in September have gone OVER the total points line.
Eleven of the Chargers’ last 12 road games in September have gone UNDER the total points line.
Buffalo Bills Player Prop Facts
Josh Allen has scored the last touchdown in each of the Bills’ last three regular season games as favorites against AFC West opponents.
Josh Allen has scored two touchdowns in three of the Bills’ last four games.
James Cook has recorded 85+ rushing yards in each of the Bills’ last four games against AFC West opponents.
Dawson Knox has recorded 15+ receiving yards in each of the Bills’ last 10 Sunday games played on the East Coast.
Josh Allen has recorded 22+ completions in each of the Bills’ last seven September home games against AFC opponents.
Josh Allen has recorded 248+ passing yards in each of the Bills’ last five games with a total points line of at least 50.0.
James Cook has recorded 102+ rushing and receiving yards in each of the Bills’ last five home games with a total points line of at least 50.0.
James Cook has scored at least one touchdown in seven of the Bills’ last eight games against teams on a losing streak.
Heading into Week 3, Gregory Rousseau ranks 1st in the NFL in sacks (4.0) this season.
Los Angeles Chargers Player Prop Facts
Justin Herbert has recorded 229+ passing yards in 10 of the Chargers’ last 11 games with a total points line of at least 50.0.
Quentin Johnston has recorded 48+ receiving yards in seven of his last eight regular season road appearances.
Keaton Mitchell has recorded 24+ rushing yards in five of his last six appearances following a loss.
Omarion Hampton has scored a touchdown in each of his last four regular season appearances.
Justin Herbert has recorded 20+ completions in each of the Chargers’ last 12 games with a total points line of at least 50.0.
Quentin Johnston has recorded 48+ rushing and receiving yards in seven of his last eight regular season road appearances.
Heading into Week 3, Omarion Hampton ranks 1st in the NFL in broken tackles (7) this season.
Matchup/League Facts
Bills – four different players have recorded 50+ receiving yards in a game this season – equal-most in the NFL, heading into Week 3.
Bills – two different players have recorded 90+ receiving yards in a game this season – equal-most in the NFL, heading into Week 3.
Heading into Week 3, the Chargers have lost the second quarter in each of their last two games – equal-longest active streak in the league.
Heading into Week 3, the Chargers have lost the fourth quarter in each of their last two games – equal-longest active streak in the league.
Los Angeles Chargers vs. Buffalo Bills Prediction
I’m on the Bills in this one. I think one of the most important things to do early in the year is not overreact, but there’s no overreacting to how poor the Chargers have looked so far this season through their first two games. The Bills on the other hand have looked solid so far and until the Chargers show a sign of life, I have to keep fading them. Give me the Bills.
