Detroit (1-0) and Buffalo (1-0) have been consistent playoff contenders in recent seasons but the Lions missed the postseason in 2025 after an injury-ravaged campaign. Dan Campbell’s troops then rode their luck in Week 1, as they threw away a 21-0 lead over New Orleans deep into the third quarter and were taken to overtime. The Lions eventually prevailed 31-30 thanks to a botched two-point conversion from the Saints but it was hardly a convincing showing from the NFC North franchise.
Buffalo also made hard work of its opener, staggering to a 36-31 win over the Texans. Josh Allen got his team over the line with a 34-yard touchdown pass to Josh Palmer with 1:36 remaining in the fourth quarter. Allen finished his season debut with 20-29 completions, 334 yards and two TDs in the air while also picking up two rushing TDs. Will Allen prevail again on Thursday? Or will Detroit’s resurgence start with an upset win? Read on to find out more about this huge NFL matchup
Detroit Lions vs Buffalo Bills Predictions, Picks & Odds - 8:15pm - 9/17/2026
- Lions +4.5 @ -110 with BET99
- Over 53.5 @ -125 with BET99
- Jahmyr Gibbs 1.5+ TDs for Lions @ +185 with BET99
All odds are courtesy of BET99, correct at the the time of publishing and subject to change.
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Lions to cover on the road - Lions +4.5
For all their talent, the Bills are not a team that always finds it easy to run up big scores when backed by the oddsmakers. Buffalo finished 6-9 ATS as favorite in 2025 and 4-5 ATS when playing at home. Playing their first match at the new Highmark Stadium, the Bills will not have an easy run either against the Lions.
Detroit was far from its best against New Orleans but pulled through on the back of an excellent game from Jahmyr Gibbs. The RB carried for 156 yards and two TDs to take down the Saints. He will be encouraged by Buffalo’s weakness against the running game: the Bills gave up 133.6 yards per game on the ground last year, If Gibbs can get moving again and Jared Goff finds his range, this could be a great matchup for the Lions on the road.
- Lions vs Bills Pick 1: Lions +4.5 @ -110 with BET99
Points a plenty in Buffalo - Over 53.5 points
These are two of the very best offensive units in all of the NFL. Buffalo ranked third in the league with an average of 378.2 yards per game, just ahead of Detroit who placed fifth averaging 374.2 yards per game. And with both of these sides happy to give up points as long as they are outscoring opponents at the other end, the over looks like a smart bet here.
Detroit and Buffalo each started the season by hitting the over against the Saints and Texans respectively, both showing off early defensive fragility by shipping 30+ points against two teams not exactly not for their offensive potency. The Lions went 10-7 on the over last season while the Bills finished with an O/U record of 10-8-1, going 5-2 when rated as the home favorite. With Goff and Allen settling quickly and those aforementioned wobbles out of possessions, bank on a big score this Thursday.
- Lions vs Bills Pick 2: Over 53.5 points @ -125 with BET99
Jahmyr Gibbs 1.5+ TDs for Lions
Could Gibbs really post up back-to-back multiple TD games to start the season? The Lions RB was on fire against the Saints, essentially keeping Detroit in the game after the favorite stalled in the third quarter. And with the Bills’ relative weakness on the ground Gibbs looks like a great bet to dominate against much tougher opposition. The Lions remain prolific inside the Red Zone - they ranked 8th in 2025 with a 62.5 RZ conversion percentage, after placing third with almost 68% success in 2024 - and they will look to get the ball to Gibbs as much as possible with the line in sight on Thursday.
- Lions vs Bills Pick 3: Jahmyr Gibbs 1.5+ TDs for Lions @ +185 with Sports Interaction
Detroit Lions vs Buffalo Bills Start Time
Thursday marks a special day for the Buffalo Bills as they play their first-ever regular season NFL game at the new Highmark Stadium. The Lions are in town for this landmark occasion and will not be keen to leave empty-handed, though, following their disappointing 2025. Both of these teams made a winning start in Week 1, setting up a fascinating AFC-NFC matchup in Upstate New York.
Detroit Lions vs Buffalo Bills Game Details
- Start Time: 8:15pm ET
- Location: Highmark Stadium
- Address: One Bills Drive Orchard Park, NY.
- Streaming: NFL+ (Worldwide)