Below, bettors can find NFL odds and a Bills vs Lions prediction for Week 2’s TNF contest in Buffalo’s home opener.
Bills vs Lions Odds, Spread & Over/Under for Week 2
Lions vs Bills Prediction
Based on the situational spot for the Lions defense and Buffalo’s prior success against this unit, my Bills vs Lions prediction is the Bills Over 29.5 Points (-120).
It’s a high number to clear on short rest, but that’s how little faith I have in this Detroit defense.
In the first half, the Lions caused havoc on the Saints as a seven-point home favorite. But the unit crumbled in the second half. Kelvin Sheppard’s defense allowed 24 points before overtime.
More concerning is that the Lions now face a short-week road game after playing an extra period. Buffalo faces a return trip home after playing in Houston, but they’ll start fresher.
For the Detroit defense, it’s a sizable step up in competition based on last year’s metrics.
New Orleans – across the entire 2025 season – finished 27th in offensive DVOA, per FTN Fantasy. Buffalo finished fourth at +15.1%, including second on the ground.
Additionally, Detroit will operate without Kerby Joseph and Brian Branch. With those two set to miss at least the first four games, it leaves a very inexperienced secondary to face Josh Allen.
Bettors should also consider prior games between these two teams.
During the 2024 NFL season, Buffalo traveled to Detroit and racked up 47 points against a unit that included Joseph & Branch. Allen posted his best PFF passing grade of the season.
From Buffalo’s standpoint, the offense impressed me against the Texans. Against a comparably more difficult unit, the Bills scored 36 points.
While a case exists for negative regression – Buffalo achieved that output on only three red zone trips – it’s my belief that regression fails to arrive in this spot.
Lastly, Buffalo’s defense concerns me enough that they’ll need to score 30 here to win. Pair that with their historical success against Detroit, and I predict the Bills offense clears a high number.
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