My NFL picks for Lions vs. Bills on Thursday Night Football back Detroit to cover as road underdogs in a high-scoring shootout at the new Highmark Stadium. Sign up with our bet365 bonus code and grab $365 in bonus bets when your $10+ first bet settles today, Sept. 17, 2026.
Buffalo opens its brand new Highmark Stadium at 8:15 p.m. ET on Prime Video, and NFL pdds have the Bills as 4.5 point favorites over Detroit. Both teams arrive 1-0 after chaotic Week 1 finishes. Both defenses also leaked points in the process. That combination steers my card of NFL picks straight toward the road underdog and the Over.
My Lions vs. Bills NFL Picks
| Pick | Market | bet365 Price |
|---|---|---|
| Lions +4.5 | Spread | -115 |
| Over 54.5 total points | Total | -110 |
| Josh Allen anytime touchdown | Player prop | -140 |
| Jahmyr Gibbs over 90.5 rushing yards | Player prop | -110 |
| Final score: Bills 31, Lions 28 | Prediction | N/A |
Explaining My NFL picks
The Lions travel with enough offense to trade haymakers with Buffalo, but bet365 Sportsbook prices this game as if only one side owns a real defense, when in reality, neither side does after one week of tape.
- Detroit scores in bunches. Jahmyr Gibbs pounded New Orleans for 156 yards and two touchdowns on 29 carries, and Jared Goff added two passing scores in a 31-30 overtime win last week.
- Buffalo surrendered 31 points at home to a Houston offense that fought for every yard all of last season. A dropped interception late saved the Bills from a 1-0 hole.
- I expect Detroit to answers after nearly coughing up a 21 point lead and set the tone for their first prime time trip of the season.
- I like the Lions to cover as a live dog as Detroit sits 5-1 against the spread across its last six games as an underdog of more than three points.
Buffalo deserves respect in their new building, with Josh Allen, 2025 rushing champion James Cook and new target DJ Moore under rookie head coach Joe Brady. Respect the Bills on the moneyline. But take the Lions' points on the spread.
Why the Over Anchors My NFL picks
Two offenses in rhythm, two defenses searching for answers, and one loud building all combine to form my Lions vs. Bills NFL picks. The totals market sits too low for what these rosters put on tape.
- These teams combined for 67 points in Week 1.
- Buffalo averaged 7.9 yards per play against one of the league's stingiest defenses.
- Detroit let Tyler Shough throw for 410 yards and three touchdowns in the second half.
- The last meeting between these teams produced a 48-42 Buffalo win, 1,101 total yards and 90 combined points.
- The Over cashed in both Week 1 games for these clubs.
Lions vs. Bills Predictions: Player Props Worth a Look
- Josh Allen anytime touchdown. Allen punched in two rushing scores at Houston and owns the goal line in Buffalo's offense. Opening night in a new stadium invites exactly that kind of moment.
- Jahmyr Gibbs over rushing yards. Gibbs handled 29 carries in the opener, a workload that signals a featured role. Buffalo gave up chunk runs in Houston.
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