The Detroit Lions and Buffalo Bills are both 1-0, and both scored 30-plus points in Week 1. Now they meet on Thursday Night Football in the first regular-season game at Buffalo’s new Highmark Stadium. The market has moved hard toward the home side since the line opened. Buffalo now sits as a 5.5-point favorite with a total of 55. Detroit, meanwhile, arrives on a short week without two starting offensive linemen. Below, we break down the injury news, line movement and public split before delivering our spread and total picks.
Last Updated: Thursday, September 17, 2026
Detroit Lions vs. Buffalo Bills — Time & How to Watch
| Where | Highmark Stadium, Orchard Park, NY |
| When | Thursday, September 17 – 8:15 PM ET |
| TV | Prime Video |
Detroit Lions vs. Buffalo Bills Betting Preview
Buffalo opened the Joe Brady era with a 36-31 road win over Houston. Brady made his head coaching debut, and Josh Allen carried the offense. The former MVP completed 20 of 29 passes for 334 yards and two touchdowns. He also ran for two more scores. His 34-yard touchdown pass to Joshua Palmer with 1:36 left put the Bills ahead for good. Still, the Buffalo defense allowed 31 points. For more on that opener, see our Bills vs. Texans prediction.
Detroit needed overtime to escape New Orleans, 31-30. Jared Goff completed 26 of 39 passes for 206 yards and two touchdowns without an interception. Jahmyr Gibbs did the heavy lifting with 29 carries for 156 yards and two scores. Amon-Ra St. Brown caught both touchdown passes, including the go-ahead score in overtime. The Lions then stopped a Saints two-point try to seal it. However, the defense also let Tyler Shough throw for 410 yards as New Orleans rallied from a 21-point hole. Detroit is coming off a three-takeaway effort, and it may need more of the same on the road.
The injury report is the bigger story. The Lions ruled out starting right tackle Blake Miller and starting left guard Christian Mahogany. Ben Bartch, who played most of the Saints game at left guard, is set to start there. Cornerback D.J. Reed is questionable with a foot injury. For Buffalo, safety Cole Bishop, running back Ty Johnson and defensive lineman T.J. Sanders are all questionable. Both starting quarterbacks, Allen and Goff, carry no injury designation.
These teams last met in December 2024, when Buffalo won a 48-42 shootout at Ford Field. Detroit went 9-8 last season and missed the playoffs. Buffalo, meanwhile, also features running back James Cook, who won the 2025 NFL rushing title.
Detroit Lions vs. Buffalo Bills Odds
| Spread | Moneyline | Total | |
|---|---|---|---|
| Lions | +5.5 (-110) | +205 | O 55 (-115) |
| Bills | -5.5 (-110) | -245 | U 55 (-105) |
Odds accurate as of Thursday, September 17, 2026 via TheSpread.com. Odds change, get the latest NFL Odds – Futures – Props
Detroit Lions vs. Buffalo Bills — Who Is the Public Betting?
| Lions | 64% | 36% | Bills |
See the latest NFL Public Betting Splits and make smarter wagers!
Lions vs. Bills Prediction — Is the Market Telling Us Something the Public Isn’t?
This line opened with Buffalo laying just 3 points. It now sits at 5.5, well past the most important number in NFL betting. The moneyline moved the same way, from Bills -160 to -245. That -245 price implies roughly a 71 percent chance of a Buffalo win. Meanwhile, 64 percent of spread bets are on Detroit. When the number climbs toward the side taking fewer bets, it usually means the larger money disagrees with the crowd. Our Lions vs. Bills odds and public betting preview tracked that split earlier in the week.
The injury news explains much of the move. Detroit will play on a short road week with two new starters on the offensive line. In addition, the home crowd will be loud for the first regular-season game in the new building.
The case against is real, though. A 5.5-point spread gives the underdog plenty of room. Detroit can shorten the game with Gibbs, who just carried the ball 29 times. The Lions also forced three turnovers in Week 1, and one extra possession swings a number like this. Still, backup linemen, a short week and a raw road environment are a tough mix. We side with the move.
The Pick: Bills -5.5 (-110)
Lions vs. Bills Prediction — Can Both Offenses Keep Rolling on a Short Week?
The total has climbed from 52.5 at open to 55. Both defenses gave up 30-plus points in Week 1, and both offenses produced big plays. Allen averaged more than 11 yards per pass attempt in Houston. Detroit, meanwhile, got 156 rushing yards from Gibbs. The last meeting between these teams produced 90 points. Rosters have changed since, but both offenses can trade scores.
On the other hand, the market has already priced much of this in. A Thursday game after a Sunday opener can produce sloppy execution. Detroit’s patched-up line could also stall drives and bleed clock with Gibbs. That would work against the number. Still, a Buffalo offense this efficient at home can push the pace on its own, and Detroit has shown it can answer. We lean toward points.
The Pick: Over 55 (-115)
Final Thoughts and Bonus Angle
We are passing on a bonus play here. The Bills moneyline at -245 already asks a lot, and the Lions at +205 need a clean game from a reshuffled offensive line. Neither price stands out enough to add. Instead, the value sits with the spread and total, where the line movement and injury news point in a clear direction.
Here is a recap of our Lions vs. Bills picks:
- Bills -5.5 (-110)
- Over 55 (-115)
NFL Lions vs. Bills FAQ: Thursday September 17, 2026
What time does the Lions vs. Bills game start?
The Lions vs. Bills game kicks off at 8:15 PM ET on Thursday, September 17, 2026. It is a Week 2 matchup and the first regular-season game at Buffalo’s new Highmark Stadium. Both teams enter the night with 1-0 records after winning their season openers on Sunday.
What channel is the Lions vs. Bills game on?
The Lions vs. Bills game airs on Prime Video as part of Thursday Night Football. Amazon holds exclusive national rights to the Thursday package. Fans in the Detroit and Buffalo home markets can also watch on local over-the-air stations, per Amazon’s broadcast announcement.
How can I stream the Lions vs. Bills game?
You can stream the Lions vs. Bills game on Prime Video, which carries the game exclusively for national viewers. Amazon is also streaming the broadcast live on its Prime Video channel on Twitch. Kickoff for this Week 2 matchup between two 1-0 teams is set for 8:15 PM ET on Thursday.
Where are the Lions and Bills playing?
The Lions and Bills are playing at Highmark Stadium in Orchard Park, New York. This is the Bills’ new stadium, and Thursday’s game is its first regular-season contest. Kickoff is set for 8:15 PM ET, with both teams entering Week 2 at 1-0.
Who won the last meeting between the Lions and Bills?
The Bills won the last meeting between the teams, beating the Lions 48-42 on December 15, 2024, at Ford Field in Detroit. The high-scoring Week 15 game combined for 90 points, and Thursday marks the first matchup between the clubs since then.