Both teams are coming off Week 1 wins after the Lions defeated the New Orleans Saints in the league's first overtime game of the season, while the Bills forced a last-minute turnover to hold off the Houston Texans 36-31.
The second Thursday night matchup of the year will officially mark the first regular season game at Buffalo's new Highmark Stadium.
Bills-Lions history
Dating back to 2010, the Bills have won all five of their matchups against the Lions, with each one being decided by six points or less. Their most recent was in 2024 when the Bills beat the Lions in a 48-42 shootout with 1,080 total combined yards, 58 first downs, 11 penalties, and only one turnover (DET) between both teams.
Each of the six drives in the fourth quarter alone ended in a scoring play, all three of Detroit's being a touchdown. Fans can even re-watch the full game over on YouTube.
Buffalo holds an 8-4-1 all-time record against the Lions (3-0 with Josh Allen under center) and have outscored them 274-273 in those matchups dating back to 1972.
Bills breakdown
Josh Allen was one of five quarterbacks in the entire league to throw for more than 300 passing yards last week. He enters the game with the third-highest passer rating (130.5) after completing 20 of 29 passes for 334 yards and two touchdowns.
Buffalo took a sigh of relief after Allen tossed a prayer to Joshua Palmer with under two minutes left in the game that was dropped by Texans cornerback Kamari Lassiter. Had Lassiter caught it, the Bills would be looking at a 31-30 loss and a 0-1 record.
However, Allen found Palmer again for a 34-yard touchdown and his only catch of the game that eventually won them the game.
On the ensuing drive, Texans QB C.J. Stroud was stripped by Greg Rousseau as the Bills recovered to end the game.
The Bills defense still has some kinks to be worked out. Before his last-minute blunder, Stroud put up 289 total yards and two touchdowns against them, while running backs David Montgomery and Woody Marks combined for 102 yards and two touchdowns on 29 carries.
But they did force three sacks and two fumbles on Stroud. And with a Lions offensive line that will be missing three of their five starters, the Bills defensive line might have a Thursday night feast.
The Bills enter the Week 2 matchup with the sixth-ranked offense and a 23rd-ranked defense that'll be looking to lock down Lions running back Jahmyr Gibbs, who has the second-most scrimmage yards (186) entering Week 2.
They'll look to make it three straight seasons of going 2-0 through the first two weeks.
This'll mark Joe Brady's first Thursday Night Football showdown as the team's new head coach. He'll look to rely on Allen, who currently holds an 8-1 record on Thursday night and a 21-8 overall record in primetime.
Buffalo will be wearing their classic home uniform for the matchup.
Lions breakdown
Much like the Bills, the Lions have their own defensive woes to worry about. They held a 21-14 lead heading into the fourth quarter against the Saints, who then scored 10 points to the Lions' three (24-24) to force OT.
After scoring first in OT, the Lions held off the Saints for a win but not without concern. Saints QB Tyler Shough tossed a Week 1-best 410 yards against the Lions secondary, including three touchdowns.
Detroit's defense did force five sacks, including two from Aidan Hutchinson, who moved up to fifth-most (45) in Lions history. They also forced two interceptions and two fumbles (one recovered), and held the Saints to just 91 yards rushing on 25 attempts (3.6 YPC).
Most importantly, they came up clutch when it mattered most.
On the offensive side, QB Jared Goff had a solid game, completing 26-of-39 passes for 205 yards and two touchdowns, both to wide receiver Aman-Ra St. Brown, who finished with 10 receptions for 67 yards.
But it was Gibbs' 156-yard, two-touchdown performance on the ground that lifted the Lions to their first win of the season.
Not too far behind Cook (1,621), Gibbs finished seventh in rushing (1,223) last season. Thanks to their Week 1 win, Detroit are now a whopping 11-0 in regular season games when Gibbs eclipses 100 rushing yards dating back to his 2023 rookie season.
Buffalo were 3-2 last season when giving up more than 100 yards to an opposing rusher, but ultimately finished with the 28th-ranked rushing defense. So if the Lions want to win the matchup, they need to get Gibbs going.
They'll also need to lock down tight end Dalton Kincaid. He not only finished first among all tight ends in Week 1 with 130 receiving yards, but ranked fifth overall among all receivers.
Detroit are looking to go 2-0 to start a regular season for the first time since 2017. In each of the past four years, they've gone 1-1 in the first two weeks.
Head coach Dan Campbell has much more experience than Joe Brady when it comes to primetime matchups. He's 13-3 overall and 3-0 on Thursday night.
The Lions will be rocking the all-white unis for the game.
Injury report
On the Buffalo Bills side, it's worth noting that Wednesday's practice was a walk-through. Safety Cole Bishop (knee/groin), running back Ty Johnson (hamstring), and defensive lineman T.J. Sanders (knee/illness) are all questionable.
Defensive back Jordan Hancock, linebacker Bradley Chubb, and linebacker Terrell Bernard have no injury status for the game.
For the Detroit Lions, offensive linemen Christian Mahogany (hip) and Blake Miller (knee) are both out, while cornerback D.J. Reed (foot) is questionable. This means that the Lions will be without three of their five starting offensive linemen (center Cade Mays on IR).
Defensive back Christian Izien (groin) and backup center Juice Scruggs (knee), who started for Mays in Week 1, are good to go for the matchup.
However, they'll be without backup running back Isiah Pacheco for an expected 12 weeks after undergoing back surgery.
Betting odds
The Bills are 5.5-point favorites over the Lions with the over/under set to 54.5. The money line has the Bills at -255 (Lions +210).
Gibbs (-300), Allen (-170), and Cook (-130) are the top three favorites to score a touchdown, with Hutchinson (-160) and Rousseau (-108) as the favorites to record at least one sack.
The first touchdown scorer for either side is split between Gibbs and Cook (+185), then Gibbs and Allen behind at +200.
St. Brown's over/under for receiving yards is at 79.5, while Moore's is at 63.5.
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