The Buffalo Bills host the Detroit Lions in the Week 2 edition of NFL Thursday Night Football on Sept. 17. Kickoff from the new Highmark Stadium in Orchard Park, N.Y., is set for 8:15 p.m. ET. TNF will stream live on Prime Video.
The Bills are 5.5-point favorites over the Lions on the spread (Bills -5.5), with an over/under of 54.5. Buffalo is a -255 favorite on the moneyline and Detroit is a +210 underdog.
Continue below for our Lions vs Bills picks for Thursday Night Football, which include predictions for the spread, over/under, and three player props.
Lions vs Bills Picks, Props
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Specific betting recommendations come from the sportsbook offering preferred odds as of writing. Always shop for the best price using our NFL Odds page, which automatically surfaces the best lines for every game. | ||
Lions vs Bills Odds
- Lions vs Bills Moneyline: Lions +210, Bills -255
- Lions vs Bills Total: 54.5 (-114o / -106u)
- Lions vs Bills Spread: Lions +5.5 (-108), Bills -5.5 (-112)
For the latest from sportsbooks nationwide, check out VegasInsider's NFL Week 2 Odds & Action Report.
Lions vs Bills Spread Prediction
The NFL began their early season Thursday night football slate in 2012. Since that point, underdogs of more than a field goal are 6-2 against the spread (ATS) in Week 2 on Thursday, specifically.
Furthermore, in Week 2, all road underdogs have fared extremely well in recent years. Over the last five seasons, road teams playing as an underdog of more than a field goal are 24-11 against the number, covering at a 68.6% rate.
This is only one data point that supports the Lions making Thursday Night Football a highly competitive game.
The Bills defense has plenty of unanswered questions and I am not convinced they can consistently stop the run despite their performance against Houston in Week 1. Detroit had the highest rushing success rate league-wide a week ago against an improved Saints defense and should have the upper-hand once more against a Buffalo defense that ranked 30th in yards per carry in 2025.
The Lions may have surrendered a league high in passing yards to Tyler Shough on Sunday, but their yards per attempt allowed still bested what Buffalo yielded to C.J. Stroud.
The Lions were able to create pressure at a 40.6% rate. Only nine defensive units generated pressure at or above 40% in Week 1 and those teams went 9-0 straight up and 7-2 ATS.
I expect Josh Allen to lead several scoring drives, but his reckless play combined with the Bills' aggressive approach with Joe Brady as head coach should give the Detroit defense some opportunities for takeaways. The Lions will turn any turnovers into points if they are gifted short fields.
Don’t be surprised when this game goes down to the wire.
I’d play the Lions down to +4 in what has historically been a very good week to back road underdogs.
Pick: Lions +5.5 (-102); bet to +4
Lions vs Bills Over/Under Pick
By Billy Ward
The Lions' Week 1 game against the Saints had just seven first-half points as both teams took some time to get going – yet still finished above 60 points as the second half turned into a shootout at Ford Field.
That result confirmed my fears about the Lions defense: they’re capable of making big plays (five sacks, two interceptions) but equally vulnerable to getting picked apart.
They were picked apart at the hands of Tyler Shough, who threw for over 400 yards and three touchdowns. Shough is an improving young QB, but certainly no Josh Allen.
The 2024 MVP contributed four touchdowns total (two passing, two rushing) against last year’s No. 1 defense in the Texans. The Lions defense should get better this year if they get either of their top safeties back, but are unlikely to get to Houston’s level.
At the same time, the Bills allowed 31 points to the Texans, who projected as a lower tier offense in the preseason. If Houston can do that to the Bills, the Lions certainly should be able to, especially since the notoriously weather-adverse team is catching the Bills while it’s still 70 degrees and clear in Buffalo.
At the end of the day, we have two of the league's top offenses taking on two poor defenses, with coaching staffs willing to push the pace if need be.
The slow start in Week 1 for the Lions was in part due to Dan Campbell and company leaning on the run with a 7-0 lead for much of the first half, but they’re smart enough to stay aggressive against the Bills in any game script.
Similarly, the Bills are unlikely to sit on a lead after needing a late touchdown to win a game they had led by 10 shortly before halftime.
Pick: Over 54.5 (-108 to -115)
Josh Allen Interception Props
Josh Allen looked great in the Bills' Week 1 win over the Texans, but he was lucky to escape that game without an interception. The Texans forced Allen into two turnover-worthy-plays and one was dropped in the end zone
The Lions' defensive front is a bit underrated and their pressure forced Tyler Shough to throw two interceptions in the first half last week.
I think the Lions can get some pressure on Allen, especially if they blitz at a 40% rate again like they did in the opener.
I have this closer to a coinflip so at +140, this works for me!
Pick: Josh Allen Interception (+140)
Dalton Kincaid Receiving Yards Prop
By Brit Devine
The books are not reacting fast enough to Dalton Kincaid's performance in Week 1.
Kincaid led all TEs last season (minimum five games played) in yards per route run and was behind only Jaxon Smith-Njigba and Puka Nacua amongst all skill-position players.
Between injuries and former head coach Sean McDermott, Kincaid's only problem in previous seasons was getting enough snaps to be a huge performer. With new head coach Joe Brady, and Kincaid seemingly at full health, we just saw him run 22 routes on 29 Josh Allen pass attempts in Week 1.
Brady seems to be willing to give Kincaid a near full-time role in the passing game, which means we should have much higher expectations for Kincaid’s performances (when he is healthy), as he has been elite on a per-route basis since entering the league.
The Lions surrendered 410 yards in the air in an overtime game. Their defense could be in big trouble traveling on a short week to face the Bills in a game in which they are hosting their first regular-season game in their new stadium.
This one is a relatively big bet for me (3.45 units to win 3).
Pick: Dalton Kincaid Over 50.5 Receiving Yards (-115)
Dalton Kincaid Anytime Touchdown Prop
By Brit Devine
As you can see above, I'm all over Kincaid stock right now — his new full-time role is simply too good to pass up on for him to find the end zone at these odds.
This +300 that is available is a particularly egregious error by the books to open the week. I would play this to +230.
Pick: Dalton Kincaid Anytime Touchdown (+300)
