Bills vs Lions Odds, expert picks, team and player news, betting trends, and stats

The highest scoring total of Week 2 (O/U 54.5 points) resides in New York this week when the Buffalo (1-0) host the Detroit Lions (1-0) on Thursday Night Football! The last five matchups have resulted in six or fewer points, so it’s no surprise we see a -5.5 point spread. Detroit is coming off a 31-30 OT win versus New Orleans whereas Buffalo beat Houston 36-31 behind a last-minute touchdown throw by Josh Allen.

Buffalo will be playing its first game at the new Highmark Stadium and you can expect Bills fans to go all out. The Week 1 win for Buffalo was as exciting as it gets. Josh Allen threaded the needle over and over for 20-of-29 for 334 yards and two touchdowns. He also added two rushing scores in the red zone as Houston could not contain him. Allen was sacked twice, fumbled once, and should have had a game-losing interception that was dropped by Houston.

While James Cook had a quiet afternoon with 13 carries for 57 rushing yards and three receptions for 12 yards, DJ Moore and Dalton Kincaid shined. Moore caught five out of eight targets for 100 yards and a touchdown, while Dalton Kincaid had five catches on six targets for a career-high 130 yards. Buffalo’s defense forced CJ Stroud into two fumbles, including the game-sealing fumble with 16 seconds remaining.

Detroit was lucky to escape with a win in Week 1. The Lions lead the Saints 21-0 in the third quarter and couldn’t muster up much offensively with three punts and a field goal over four drives to end regulation. New Orleans didn’t convert their two-point OT conversion as the Saints attempted to go all-in during Week 1. On a positive note, the Lions 1-2 punch of Jahmyr Gibbs and Amon-Ra St. Brown had a day. Gibbs had a career-high 29 carries for 153 rushing yards and St. Brown caught 10 passes for 10 passes for 67 yards. Both players scored two touchdowns each. While the Lions could go score for score with the Bills, they are down two starting offensive line and aren’t in a great historical betting spot.

There’s a model that says teams off an OT game and playing on four days of rest or less versus another team that hasn’t played in OT the week prior are only covering at a 16.1% rate since 2000. History isn’t on Detroit’s side as they enter a new era of football at Highmark Stadium.

Let’s dive into the numbers and see if we can’t find an additional sweat or two.

NBC Sports has all the latest info and analysis you need, including how to tune in for kickoff, odds from DraftKings, player news and updates, and of course our predictions and best bets for the game from our staff of experts.

Game details and how to watch Lions at Bills

· Date: Thursday, September 17, 2026
· Time: 8:15 PM ET
· Site: Highmark Stadium
· City: Orchard Park, NY
· TV/Streaming: Prime Video

NBC Sports is your home for all the latest updates on this matchup, featuring live odds, player news, expert analysis, and predictions.

Latest Game Odds for Lions at Bills

The latest odds courtesy of DraftKings:

· Moneyline: Buffalo Bills (-250), Detroit Lions (+205)
· Spread: Bills -5.5
· Total: 54.5

The opening spread was Buffalo -3.5 and since moved to Buffalo -5.5 due to the regular season opening of Highmark Stadium and Detroit coming off an OT game. The total for this moved from 53.5 to 54.5 with a chance at 55.5 before kickoff.

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Expert picks & predictions for Bills at Lions

Vaughn Dalzell (@VmoneySports) likes Buffalo to cover the first quarter spread and the game spread:

“Detroit is in a tough spot coming off an OT win. Yes, it was only one extra possession each for the offense and defense, the Lions let the game slip away from the late and travel on a short week to face a team that has had their number in the past. Plus, it’s the home opener of a new stadium. Oddsmakers have Buffalo around -170 to -200 to score a touchdown in the first quarter. Detroit may come out shaky early and Buffalo could force their hand to be extra aggressive, which may or may not work out. I think Buffalo covers the -0.5 in the first quarter and full game -5.5 The Team Total of 30.5 probably hits the Over too.”

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Bills at Lions betting trends and stats

• Buffalo is 1-0 ATS and 1-0 to the Over
• Buffalo has won the last five meetings versus Detroit
• Buffalo was 4-5 ATS at home last season and 2-5 ATS as a home favorite
• Buffalo was 6-3 to the Over at home last season and 5-2 to the Over as a home favorite
• Detroit is 0-1 ATS and 1-0 to the Over
• Detroit was 4-5 ATS on the road last season and 2-4 ATS as a road underdog
• Detroit was 5-4 to the Under on the road last season and 4-2 to the Under as a road underdog
• Jahmyr Gibbs is coming off a career-high 29 carries and 34 total touches in Week 1 for 186 total yards and two touchdowns
• Josh Allen threw for 334 yards and two touchdowns, plus ran for 23 yards and two touchdowns last week
• James Cook had 17 touches for 69 total yards and a fumble in Week 1
• Amon-Ra St. Brown caught 10 passes for 67 yards and two touchdowns last week

Quarterback matchup for Lions at Bills

· Buffao: Josh Allen – Allen carved up the Texans defense like a turkey, but he also threw a turkey with the game on the line and luckily for Buffalo, it was a baffling dropped interception in the end zone. Allen finished the game with 356 total yards and four touchdowns with two scores through the air and two on the ground. He is the MVP favorite for a reason and could have another eye-popping stat line in the regular season home opener at the new Highmark Stadium.

· Detroit: Jared Goff – After leading Detroit to a 21-0 lead, Goff went 5-of-9 for 27 yards in the second half with three punts and a made field goal before posting an impressive OT drive where he went 4-of-5 for 42 yards and a touchdown. Detroit let off the brakes and they can’t afford to let a toenail off the brakes in Buffalo.

Bills at Lions Injury Update

• Buffalo S Cole Bishop (Knee/Groin) is questionable
• Buffalo RB Ty Johnson (Hamstring) is questionable
• Buffalo DL T.J. Sanders (Knee/Illness) is questionable
• Detroit OG Christian Mahogany (hip) is Out
• Detroit OT Blake Miller (knee) is Out
• Detroit CB D.J. Reed (foot) is questionable

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