Detroit Lions vs Buffalo Bills Picks and Prediction for Thursday September 17 2026

The Detroit Lions visit the Buffalo Bills at Highmark Stadium in Orchard Park, New York, on Thursday, September 17, 2026. Kickoff is scheduled for 8:15 PM ET with coverage on Prime Video. Both teams enter Week 2 at 1-0 after surviving high-scoring season openers. Detroit defeated New Orleans 31-30 at home, while Buffalo went on the road and beat Houston 36-31. Thursday will also mark the first regular-season game at Buffalo's new Highmark Stadium. The Bills are currently 4.5-point favorites, with Detroit at +4.5 and the total set at 53.5 points. Make sure you are up to date with our free NFL picks.

Detroit Escaped Week 1 With a Victory

Detroit opened the season with a 31-30 victory over New Orleans, but the Lions had to survive until the end. The offense produced enough explosive plays to reach 31 points, and Detroit's rushing attack gave the Lions an important source of balance. However, allowing 30 points at home immediately creates questions about how the defense will handle an even more dangerous opponent on a short week.

The Lions averaged 5.1 yards per play in their opener. Their ability to run the football could be especially important Thursday because Detroit doesn't want to turn this matchup into a possession-for-possession shootout. Sustained drives would allow the Lions to shorten the game, protect their defense and keep Buffalo's offense on the sideline. Detroit also needs to avoid falling multiple scores behind because Buffalo showed in Week 1 that it can create points quickly.

Defense is where Detroit faces its biggest challenge. The Lions surrendered more than 400 passing yards in the opener and now face a Buffalo offense that was extremely efficient in Houston. Detroit managed to survive those defensive problems against New Orleans, but allowing another opponent to consistently generate explosive plays could produce a very different outcome on the road.

Buffalo Opens Its New Stadium After Impressive Road Win

Buffalo's 36-31 victory at Houston was one of the more impressive results from the opening week. The Bills went on the road against a quality opponent and generated enough offense to win a game that required them to score into the 30s. Buffalo averaged an outstanding 7.9 yards per play, considerably better than Detroit's 5.1-yard average in its opener.

The Bills now receive the added advantage of returning home for the first regular-season game at the new Highmark Stadium. That should create an unusual atmosphere for an already significant Thursday Night Football matchup. Buffalo doesn't need the emotion surrounding the stadium opening to justify being favored, though. The Bills' Week 1 offensive efficiency provides a strong matchup advantage against a Detroit defense that had substantial difficulty slowing the passing game.

Buffalo's concern is similar to Detroit's: the defense still allowed 31 points in Week 1. The Bills can't simply assume they will overwhelm Detroit defensively, particularly against an offense capable of controlling stretches of the game on the ground. This matchup could ultimately come down to which defense can force a couple of empty possessions. Based on the opening week, Buffalo appears more capable of creating enough offensive separation to overcome those defensive shortcomings.

Detroit Lions vs Buffalo Bills Picks and Prediction

Pick: Buffalo Bills -4.5

Take the Buffalo Bills -4.5. Detroit is dangerous enough offensively to make laying more than a field goal uncomfortable, but Buffalo has several advantages. The Bills were considerably more efficient offensively in Week 1, averaging 7.9 yards per play compared with Detroit's 5.1, and they scored 36 points on the road. Detroit's difficulty defending the pass is particularly concerning against this matchup. Add Buffalo's home-field advantage and the emotion surrounding the first regular-season game at the new Highmark Stadium, and I have the Bills winning by approximately a touchdown. I would play Buffalo through -4.5, but the value becomes less attractive if the number moves beyond -6.

Pick: Over 53.5

Take the Over 53.5. Detroit's opener produced 61 combined points, while Buffalo's produced 67. Both teams scored at least 31 points, and neither defense demonstrated that it should automatically be trusted in a matchup against another capable offense. Buffalo's offensive efficiency combined with Detroit's defensive problems creates the clearest path toward the Over, but the Lions should contribute enough themselves to prevent Buffalo from needing to do everything. A projected final around Buffalo 31, Detroit 27 puts this game at 58 points and gives us room above the current number.

Final Picks: Buffalo Bills -4.5 and Over 53.5