Detroit Lions vs Buffalo Bills Prediction, 9/17/2026 NFL Picks, Best Bets & Odds Week 2

Game: Detroit Lions vs Buffalo Bills

Date: Thursday, September 17, 2026

Location: Highmark Stadium in Orchard Park, NY

TV: Prime Video

Odds-Point Spread: Lions +4.5

Total-Over-Under: 53

The Detroit Lions (1-0) are headed to Highmark Stadium on Thursday where they will take on the Buffalo Bills (1-0). Buffalo opens this game as 4.5-point favorites from oddsmakers. The over-under has been set at 53.

The Detroit Lions head into this game 1-0 so far this year. In their last contest, the Lions faced the New Orleans Saints and took home the win by a score of 31-30. Jahmyr Gibbs was the leader on the ground for the Lions with 29 carries for 156 yards (5.4 yds per attempt). Amon-Ra St. Brown held an average of 6.7 yards per catch by notching 67 yards on 10 receptions. Jared Goff finished 26-39 with 206 yards passing and 2 TDs. He had a QB rating of 96.7 and finished the contest with no interceptions. Against the rush, the Lions conceded 91 yards on 25 tries, which is 3.6 yds per run allowed. Detroit allowed 35 pass completions on 56 tries for 378 yds, and a completion percentage of 62.5%. When the final whistle blew, they tallied 72 plays which converted into 369 yds. The Detroit Lions ran the football 33 different times and compiled 165 yds, earning them an average of 5.0 yards per carry.

If you look at getting the ball into the endzone, the group from Detroit have an average of 31.0 points per outing. As a team, they are sitting at 165.0 running yards which is 5th in pro football. The Lions have collected 369 yds for the season. Detroit currently has 10 first downs as an offense, and they have been flagged for 8 infractions for 61 total yards. They have coughed up the ball 1 time. If you analyze getting in the endzone, Detroit currently has 2 touchdowns via the pass and 2 touchdowns via the run.

Concerning passing yards, the Lions have granted 378 yards, which is 32nd in pro football. They have relinquished 378.0 yards per outing by way of the pass, and are giving up a completion% of 62.5%. Overall, they have conceded 91 yards on the ground through 1 game over the course of this year. They have allowed 3 touchdowns through the air, plus 1 touchdown via the ground game. Altogether, they are giving up 469.0 yards per outing, which has them ranked 29th in professional football. They are giving up an average of 3.6 yds per run and 91.0 running yards per contest for the season. The Lions sit 22nd in professional football if you examine their opponents scoring, surrendering 30.0 points per game.

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The Bills head into this matchup 1-0 so far this season. The last time they stepped on the football field, the Bills took home the win by a final score of 36-31 when they faced the Houston Texans. Josh Allen (2 TDs) ended the game with 334 yds on 20-29 through the air while his QB rate was 130.5. He kept the ball away from the defense with no interceptions and his average yards per pass attempt was 11.5 yds. James Cook ran the football 13 times for 57 yards, walking away from the game with 4.4 yards per carry for Buffalo. Dalton Kincaid was the best receiver for the Bills, grabbing 5 footballs for 130 yds (26.0 yards per catch). Buffalo rushed the ball for 4.1 yds per carry, finishing with 86 yards on 21 attempts. The Bills finished the game with a total of 409 yds while they ran 50 plays (8.2 yds per play). The Bills passing defense conceded a completion rate of 68.4%, surrendering 257 yards on 26 out of 38 through the air. Buffalo relinquished 32 run attempts for 124 yards (3.9 yards per carry).

The Buffalo Bills average 409.0 yds per contest, putting them 6th in professional football. They have an average of 86.0 running yards per game. They have been able to earn 13 first downs offensively. The Buffalo offense has surrendered 85 total yards by way of 10 infractions, which is good for 6th in the league if you analyze helping out the opposition. This season, the Bills have racked up 323 pass yds. Concerning this team's ability to score points, the Bills sit 5th in professional football, maintaining an average of 36.0 points per game.

The Bills are giving up 31.0 points per game, putting them 25th in professional football. They have granted 2 touchdowns by way of the pass along with 257.0 passing yards per game, which is 25th in pro football. Buffalo has allowed a total of 124 rushing yds. The Bills defense has participated in 73 plays from the line of scrimmage, putting them 31st in professional football. Their defense has attained 2 takeaways this season. All in all, they have relinquished 31 pts.

Who will win tonight's Lions-Bills NFL game against the spread?

Tony's Pick: Take the Lions +4.5

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