Lions vs. Bills Picks, Predictions & Odds for Thursday Night Football

The Detroit Lions and Buffalo Bills meet on Thursday night in one of the marquee matchups of NFL Week 2, with Buffalo opening the doors to its new Highmark Stadium for the first regular season game at the venue. Kickoff is scheduled for 8:15 p.m. ET on Prime Video.

Both teams arrive at 1-0 after surviving dramatic season openers just four days ago. Detroit needed overtime to beat New Orleans 31-30 at Ford Field, while Buffalo escaped Houston with a 36-31 victory in Joe Brady‘s first game as head coach.

The Lions appeared to be in complete control Sunday after building a 21-0 lead, but New Orleans erased the deficit and forced overtime. Jared Goff eventually led a 70-yard touchdown drive to open OT, finding Amon-Ra St. Brown for a four-yard score before Detroit’s defense stopped the Saints on a potential game-winning two-point conversion.

Detroit now faces a considerably different challenge on a short week. The Lions will be the first visiting team to play a regular season game at Buffalo’s new stadium, and they’ll make the trip with concerns along the offensive line. Starting guard Christian Mahogany and tackle Blake Miller have both been ruled out, while Juice Scruggs fully participated in practice on Wednesday after dealing with a knee issue earlier in the week.

Buffalo had its own tense opener in Houston. The Bills trailed 31-30 late in the fourth quarter before Josh Allen led a 96-yard go-ahead drive, capping it off with a 34-yard touchdown pass to Joshua Palmer. Allen threw for 334 yards and two touchdowns while adding two more scores on the ground.

The Bills also received an immediate contribution from offseason addition DJ Moore, who caught five passes for 100 yards and a touchdown in his Buffalo debut. Dalton Kincaid added 130 receiving yards as Allen repeatedly pushed the ball downfield against Houston.

Thursday night also brings together two teams trying to rebound from disappointing 2025 seasons. Detroit finished 9-8 and missed the playoffs after consecutive NFC North titles, while Buffalo went 12-5 before its postseason ended in the Divisional Round. The Bills then promoted Brady to replace Sean McDermott, beginning a new era around Allen while preparing to move into their new home.

Their most recent meeting produced one of the highest-scoring games of the 2024 season, with Buffalo beating Detroit 48-42 at Ford Field. Goff threw for 494 yards and five touchdowns in that game, while Allen finished with 362 passing yards and four total touchdowns.

Lions vs. Bills Odds Today

Buffalo will unveil its new home as a respectable favorite at Hard Rock Bet Sportsbook:

• Moneyline: Lions +195, Bills -240
• Spread: Lions +5.5 (-110), Bills -5.5 (-110)
• Total: Over 55 (-110), Under 55 (-110)

Referenced odds are subject to change.

Best Bet for Lions vs. Bills

Hard Rock Bet’s Stats Hub provides team trends, streaks and matchup data for every game throughout the NFL season. With two explosive offenses meeting on Thursday night, we’re looking the other way on a lofty total:

Under 55 (-110): Detroit and Buffalo each put more than 30 points on the board in Week 1, but there are several reasons to expect a different type of game on the short turnaround.

Both teams are coming off emotional victories that went down to the final moments, and Detroit had the more demanding afternoon of the two. The Lions played a full overtime period against New Orleans before finally securing a 31-30 win, then had only a few days to recover before traveling to Buffalo for their first road game of the season.

That turnaround becomes even more significant because of Detroit’s offensive line situation. Mahogany and Miller have both been ruled out, forcing the Lions to reshuffle a unit that will have to protect Goff and create running lanes for Gibbs in what should be one of the loudest environments they’ll see all season.

Buffalo will be dealing with plenty of emotion of its own. Thursday marks the first regular season game at the new Highmark Stadium, giving the Bills a unique homefield atmosphere for the opening night of the Thursday Night Football schedule. That doesn’t necessarily mean a slow game, but it does create another high-intensity setting for two teams already working through an unusually short recovery window.

The offenses are talented enough to make this uncomfortable, especially with Allen, Gibbs, St. Brown and Moore all capable of producing explosive plays. But at a total of 55, this game doesn’t need to become a defensive struggle for the Under to cash. With Detroit coming off overtime, traveling on short rest and missing multiple starters up front, Under 55 is the Best Bet for Thursday night.

• Best Bet: Under 55 (-110)

Betting Splits at Hard Rock Bet

Hard Rock Bet players have leaned heavily toward Buffalo, while the Over has attracted nearly all of the early action on the total:

• Moneyline: Buffalo accounts for approximately 83% of all moneyline tickets and 83.3% of the handle.
• Spread: Bills -5.5 has drawn 63.4% of spread tickets and 67% of the money.
• Total: Over 55 is the most one-sided market of the three, accounting for approximately 96% of the bets and 93.8% of the handle.

Top 5 Most-Bet Player Props for DET-BUF

Touchdown markets headline Thursday night’s most-bet player props, with Gibbs leading the group despite his heavy price to score:

1. Jahmyr Gibbs – Over 0.5 Anytime Touchdowns
2. Josh Allen – Over 0.5 Anytime Touchdowns
3. James Cook III – Over 0.5 Anytime Touchdowns
4. Amon-Ra St. Brown – Over 0.5 Anytime Touchdowns
5. DJ Moore – Over 0.5 Anytime Touchdowns

Lions vs. Bills Game Info

• 📍 Where: Highmark Stadium, Orchard Park, New York
• 📅 Date: Thursday, September 17
• ⏰ Kickoff: 8:15 p.m. ET
• 📺💻 TV/Streaming: Prime Video

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