Herbert, Harbaugh Take on Buffalo: Chargers vs. Bills – NFL Expert Picks & Predictions (9/27)
Written by: Nate Hornung
Published: Wed Sep 23, 2026, 4:30 pm ET
Read Time: 5 minutes
nfl
Spread
Total
Moneyline
+7.5
-115
50.5
-105u
+275
Spread
Total
Moneyline
-7.0
-110
50
-110o
-340
Things are looking grim in the City of Angels. Jim Harbaugh and the Los Angeles Chargers are off to an 0-2 start, after being upset twice at home, closing at about a touchdown favorite. The Arizona Cardinals and Las Vegas Raiders both left LA with an outright win, leaving Chargers fans wondering if their season is already over. It doesn't get easier this week, as they head up north to take on the 2-0 Buffalo Bills. Will Joe Brady and Josh Allen hand Harbaugh and Justin Herbert their third straight loss to start off the year? Find out below with our NFL expert picks.
Los Angeles Chargers vs. Buffalo Bills Game Information
Has Justin Herbert been too focused on his new fiancée instead of winning football games?
Matchup Information – Los Angeles vs. Buffalo – September 27
- Venue & Location: Highmark Stadium (Orchard Park, NY)
- Date: Sunday, September 27, 2026
- Kick Off: 1:00 p.m. Eastern
- Broadcast: FOX
Chargers vs. Bills Betting Odds
Odds courtesy of BetOnline as of Wednesday, September 23, 2026 at 3:46 p.m. eastern.
Spread
- Chargers +7.5 (-116)
- Bills -7.5 (-104)
Moneyline
- Chargers +278
- Bills -345
Total
- Over 50.5 (-105)
- Under 50.5 (-115)
Chargers vs. Bills NFL Analysis and Insights
Everyone's talked about the Chargers upcoming schedule, but of course I have to as well. After losing to the Cardinals and Raiders at home, this is what LA fans can look forward to after a trip to Buffalo this week.
- Week 4: @ Seattle
- Week 5: vs. Denver
- Week 6: @ Kansas City
- Week 7: BYE
- Week 8: @ Los Angeles (Rams)
- Week 9: vs. Houston
- Week 10: @ Baltimore
Finally, in Week 11 you host the New York Jets, but there is a very real chance the Chargers could be 0-9 at that point. At best, maybe 3-6 is on the table, but it's going to take a miracle. While there are smart people in this space telling you to bet the Chargers plus the points this week, possibly even outright, I can't get behind it.
I'm not rushing to back the other side, but I do think the Bills' success continues at home, even with a tough divisional game next week.
Los Angeles Chargers vs. Buffalo Bills NFL Picks
Josh Allen has been responsible for nine Bills' touchdowns already this season. Will he keep it up against the Chargers?
Best Bet: Buffalo Bills 1H Team Total Over 14.5 (+100) BetOnline
I think the Bills will have motivation to run up the score early, and rest in the second half as they prep for the Patriots coming to town next Sunday. Therefore, I am looking for them to score often in the first half, at least three times, twice for touchdowns. Their full game team total is listed at 28.5, coming down from 29.5, which I also endorse. But there may be a reason to wait and see if this dips below two touchdowns. I highly doubt it, but if you are taking the 14.5 with me, make sure you get a plus sign.
Teams have started out hot against the Chargers. The Cardinals went for 393 total yards and didn't turn the ball over. They scored 13 first half points, scoring on three of four drives in the first half, missing a field goal which would've cleared this number. Arizona also scored on four of their first five drives overall, and did not have a three and out until the fourth quarter. Last week, the Raiders produced 305 total yards with one first quarter interception. They still scored 10 in the first half, finding points on just two of their six first half drives. The others resulted in two punts, an interception, and a turnover on downs.
Point being, I think the Bills will have no trouble early on. Maybe the Chargers make adjustments at halftime, but until someone can slow down Allen and company, I'll back them to find the promised land. They scored four times for 24 points in Houston in Week 1, and did the same for 27 points against the Lions at home last Thursday.
Given the extra rest as well, I anticipate the Bills come out firing this weekend. With all that being said, Josh Allen is bound to throw his first interception of the season at some point, and it's listed at +125 this Sunday.
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Nate has been a recreational sports bettor for about 5 years. In that time, he has grown to love the pursuit of winners and sticking it to The Man. Nate loves data and uses his understanding of numbers to help him be a more profitable sports gambler, however he will be the first to tell you this game is about more than just stats.
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