Detroit Lions vs Buffalo Bills Prediction, Preview and Odds - 09/17/2026

Game Time: 8:15 pm ET, Thursday, September 17, 2026

Venue:  Highmark Stadium, Orchard Park, NY 

Where to Watch:  Prime Video

DraftKings:  Point Spread:  Lions +4.5, Bills -4.5; Over/Under:  53.5 points

Bet365:  Point Spread:  Lions +4.5, Bills -4.5; Over/Under:  53.5 points

BetMGM:  Point Spread:  Lions +4.5, Bills -4.5; Over/Under:  53.5 points

Detroit Lions:  1-0 (1st place, NFC North)

Buffalo Bills:  1-0 (1st place, AFC East)

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Detroit Lions:  won their last game at home against the New Orleans Saints 31-30 in overtime. 

Buffalo Bills:  won their last game on the road against the Houston Texans 36-31.

The Lions are entering this game with a 1-0 record overall and they have a 0-0 record in their divisional games too. They are 1-0 in their home games, 0-0 in their road games, and they are also 0-0 in their neutral site games this season, but they will be on the road for this game. They won their last game against the New Orleans Saints 31-30 in OT. Jared Goff was the starting QB and he completed 26/39 passes for 206 passing yards, 2 touchdowns, and 0 interceptions. Jahmyr Gibbs led the team in rushing yards with 156 and 2 TDs. Amon-Ra St. Brown led the receivers with 67 receiving yards on 10 receptions and 2 TDs. D.J. Reed led the defense in that game with 10 solo tackles while Aidan Hutchinson led the defense in sacks with 2. Derrick Barnes and Chuck Clark each came away with 1 interception for them in that one.

 

 

 

The Bills are entering this game with a 1-0 record overall and they have a 0-0 record in their divisional games too. They are 0-0 in their home games, 1-0 in their road games, and they are also 0-0 in their neutral site games this season, but they will be at home for this game. They won their last game against the Houston Texans 36-31. Josh Allen was the starting QB and he completed 20/29 passes for 334 passing yards, 2 touchdowns, and 0 interceptions. James Cook led the team in rushing yards with 57. Dalton Kincaid led the receivers with 130 receiving yards on 5 receptions. Terrel Bernard led the defense in that game with 12 solo tackles while Greg Rousseau led the defense in sacks with 2. No one on the defense came away with an interception for them in that one.

The current betting odds have the Bills listed as a 4.5 point favorite in this game according to Draftkings Sportsbook. The Bills have looked good in their games this season with their 1-0 record overall so far. They haven't played any home games this season and will be playing their home opener here. Meanwhile, the Lions have looked good in their games this season with their 1-0 record overall so far. They haven't played any road games though and will be playing their 1st road game of the year here. The Lions offense looked great in their season opener, but a lot of that offense was generated in the run game. Goff didn't have a great game passing and the defense still looks like it has the same major issues that they have been dealing with for years. They barely scraped by the Saints in OT with a 31-30 win at home and needed to stop a 2-point conversion just to win the game. They easily could have lost to a team that was one of the worst in the league last year and now they play their 1st road game against one of the best. The Bills are coming off a 36-31 win over the Texans in week 1 and their defense didn't look any better. They gave up 31 points to an offense that had a lot of trouble putting up points last season, but Josh Allen and the Bills offense looked great. The Bills put up 36 points against one of the best defenses in the NFL and they did it on the road in Houston where they have had a lot of trouble in recent years. The defense was still an issue, but the Texans had chances to win the game at the end and the Bills defense stepped up big to close out the game. The Lions have an offense that is going to put up points here, but the Bills have looked a lot better at home over the years, being a really tough team to beat there, and they do have the better defense to make plays when they need it most. The best way to place a bet here is on the Bills to cover the spread in this game. 

Lions Bills Prediction:  Our NFL Pick for Thursday, September 17, 2026 (8:15 pm ET start time) is Bills 31 Lions 24.

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Detroit Lions: 11-6 ATS in road games. 7-2 ATS in a road game where the total is greater than or equal to 49.5. 7-2 ATS after a game with a turnover margin of +2 or better. 12-6 OVER after scoring 30 points or more last game. 12-5 OVER after playing a game at home.

Buffalo Bills: 4-7 ATS off a road win. 23-15 OVER in all games. 11-5 OVER as a home favorite. 9-5 OVER in a home game where the total is greater than or equal to 45.5. 12-6 OVER after playing their last game on the road.

Detroit Lions:  C. Izien (CB) Questionable - Groin. T. Nowaske (LB) Injured - Knee. T. Harper (S) Injured - Ankle. E. Rakestraw Jr. (CB) Injured - Ankle. M. Wingo (DL) Injured - Groin. D. Moore (DL) Injured - Hamstring. K. Abney II (CB) Injured - Hand. J. Rolder (LB) Injured - Hamstring.

Buffalo Bills:  T. Johnson (RB) Questionable - Hamstring. J. Hancock (CB) Questionable - Quad. T. Sanders (DL) Questionable - Knee.

“We hung in there and made the last play to win and that’s the most important thing.” - Dan Campbell after his team’s win against the Saints in their last game. 

“You saw a lot of the conviction, everything we sort of talk about. We didn’t care how pretty. There’s no such thing as an ugly win.” - Joe Brady after his team’s win against the Texans in their last game. 

WR TeSlaa, Isaac

WR Williams, Jameson

WR St. Brown, Amon-Ra

TE LaPorta, Sam

QB Goff, Jared

RB Gibbs, Jahmyr

WR Coleman, Keon

WR Moore, DJ

WR Shakir, Khalil 

TE Kincaid, Dalton

QB Allen, Josh

RB Cook III, James

Passing: Jared Goff (206)

Rushing: Jahmyr Gibbs (156)

Receiving: Amon-Ra St. Brown (67)

Touchdowns: Amon-Ra St. Brown (2)

Passing: Josh Allen (334)

Rushing: James Cook III (57)

Receiving: Dalton Kincaid (130)

Touchdowns: Josh Allen (2)

Coaches:

Detroit Lions: Dan Campbell (6th season)

Buffalo Bills: Joe Brady (1st season)