Chargers vs. Bills Prediction, NFL Week 3 Odds & Picks (9/27)

Fact checked at 5:50 PM ET, Sep 26, 2026

Odds as of Sep 26, 5:30 PM ET

The Chargers arrive in Orchard Park at 0-2 after losing both home games by the same 26-14 score, first to the Cardinals as 9.5-point favorites and then to the Raiders as 6.5-point favorites. The Bills are 2-0 and covered both times, winning 36-31 at Houston and 41-31 over Detroit on Thursday, Sep 17, so they come in with three extra days of rest. Buffalo leads the league at 38.5 points per game. The Chargers' 14.0 ranks 30th.

The market has moved hard toward Buffalo, then given a little back. The Bills were -3 on the look-ahead line, opened around -7 when the Week 3 lines went up after last Sunday's games, reached -7.5 during the week and by Saturday evening were back to -7 at most books, with FanDuel and bet365 still at -7.5. The moneyline is Bills -350 and Chargers +275. The total has climbed from 48.5 to 50 at most books (50.5 at FanDuel and bet365) even though 89% of the money on the total is on the Under. The Chargers are also short-handed: guard Kayode Awosika, tight end Charlie Kolar and nose tackle Dalvin Tomlinson are out, while Buffalo receivers DJ Moore and Keon Coleman are questionable and game-time decisions.

Kickoff is Sunday at 1:00 PM ET at Highmark Stadium in Orchard Park, on FOX. The National Weather Service's Saturday afternoon forecast for the 1 PM kickoff calls for mostly cloudy skies, 66 degrees and a north wind around 9 mph, with gusts near 20 by the second half and a chance of showers mainly after 3 PM.

Chargers vs. Bills Predictions

• Pick #1: Bills -7.5 (-102)
• Pick #2: Dawson Knox Under 9.5 Receiving Yards (-113)
• Pick #3: Omarion Hampton Anytime Touchdown (-105)

PICK #1: Bills -7.5 (-102)

Buffalo has scored 36 and 41 points and the Chargers have scored 14 twice, and the line has moved toward that gap since it opened.

Buffalo was -3 on the look-ahead line and reached -7.5 during the week, a 4.5-point swing that carried it past the key number of 7, most of it before the Week 3 market opened around -7. Since then the number has drifted back: DraftKings, BetMGM, Caesars, Fanatics and BetRivers are at -7 (-112 to -115), while FanDuel (-102) and bet365 (+100) still have -7.5. If you believe in the cover, the half point at FanDuel's price is the better ticket, and that is the number we're on.

Josh Allen has thrown for 334 and 248 yards with five touchdown passes and no interceptions, and he has added two rushing touchdowns in each game. Justin Herbert has thrown for 209 and 192 yards with three interceptions, was sacked three times in each game, and the offense has converted 31.82% of its third downs, 28th in the league.

The unit that produced those numbers is now thinner. Awosika, the starting left guard, is out with a fibula injury, with Trevor Penning now listed at left guard. Kolar, the top tight end at 62% of the snaps last week, is out with a broken forearm, and David Njoku, who split the job with him in Week 1, is on injured reserve with a fibula injury. On defense, Tomlinson (hamstring) is out, and safety Elijah Molden misses a second straight game.

The case against laying 7.5 starts with Buffalo's own defense, which has allowed 31 points in both games (tied for 28th) and 300.5 passing yards a game (30th), so a late Chargers score can close the gap, and a seven-point Buffalo win loses this ticket. It's also the popular side: 90% of the moneyline bets and 68% of the spread bets are on Buffalo, and the spread money (63%) trails the tickets. Moore, Coleman and defensive tackle Ed Oliver (hip) are all questionable, and the inactives come out Sunday before kickoff. -102 puts the implied chance at 50.5%, cheaper than the -112 or worse you'd pay for -7. As for the other two picks, Knox's Under doesn't depend on the margin, and a Hampton touchdown fits inside the 14-point day the Chargers have managed twice, which still leaves Buffalo room to cover.

PICK #2: Dawson Knox Under 9.5 Receiving Yards (-113)

Knox is on the field a lot and rarely thrown to.

He has played 67% and 76% of Buffalo's offensive snaps and has 7 and 5 receiving yards to show for it, on one target and then two. His job has been blocking, next to Jackson Hawes, while Dalton Kincaid is the tight end Allen looks for: 6 and 8 targets, 130 and 95 yards.

Week 2 is the telling game. Moore left after 23 snaps, Knox's snaps rose to 76%, more than Kincaid's 66%, and he still finished with two catches for 5 yards, one of them a touchdown, on two targets to Kincaid's eight. More snaps didn't turn into more yards.

We took Knox over the bigger Buffalo props because his number is tied to his role rather than the score. Kincaid Over 56.5 receiving yards (-114) and Allen's passing props ride the same big Buffalo passing day the spread leans on, while Knox's job as a blocker holds whether Buffalo wins by three or twenty. Buffalo's receiver availability is the caveat, covered below. James Cook Under 11.5 receiving yards (-110) is the alternative, but both of Cook's games came without third-down back Ty Johnson, who practiced fully all week, carries no game designation and is expected to make his season debut.

The lack of room is the bigger worry. One catch of 10 yards beats this, and Knox reached 7 on a single catch in Week 1. If Moore and Coleman both sit, Buffalo could use more two-tight-end sets and send Knox on more routes, and the Chargers have allowed 265 passing yards a game, 25th in the league. The -113 price implies 53.1%, a small premium for two quiet games.

PICK #3: Omarion Hampton Anytime Touchdown (-105)

Every Chargers game this season has included a Hampton touchdown run, and Buffalo has allowed 31 points twice.

He carried 12 times for 43 yards and a touchdown against Arizona, then 23 times for 94 yards and a touchdown against Las Vegas. His share grew along the way, from 58% of the snaps in the opener to 63% last week, while Keaton Mitchell's slipped from 31% to 25%, with 4 and 5 carries. The Chargers have scored two touchdowns in each game, and each time one of them was a Hampton run; he has both of the team's rushing scores. Buffalo, meanwhile, has allowed 31 points to Houston and 31 more to Detroit, and defensive tackle Ed Oliver, who missed the Detroit game, is questionable again.

We picked Hampton over Justin Herbert Over 0.5 interceptions (-120) and Allen's touchdown (-140) because his role is the most settled of the three: he has every Chargers rushing score and a rising snap share, and a Hampton touchdown fits a competitive game as easily as a rout. The Herbert interception is the alternative for anyone who wants the Chargers' mistakes instead.

The price has drifted our way since the week began, from around -130 to -105 at BetMGM on Saturday, which implies 51.2%, but there are real ways to lose. Hampton has lost a fumble in each game, the kind of habit that can cost a back his goal-line carries. His blocking is thinner without Awosika, Kolar and Njoku, and Buffalo has allowed 95 rushing yards a game, 11th in the league. A big early Buffalo lead would push the Chargers toward passing, and their other two touchdowns were catches by Ladd McConkey and Oronde Gadsden. It also leans slightly against the first pick, but not by much: a 31-17 game has room for a Hampton touchdown and a Buffalo cover.

21+ (18+ where permitted). Odds subject to change. If you or someone you know has a gambling problem, call 1-800-GAMBLER.