NFL Thursday Night Football Predictions: Lions at Bills

After close wins in their season openers, the Detroit Lions and Buffalo Bills have a short turnaround in preparation for the Week 2 NFL Thursday Night Football game. Both teams enter the primetime clash after showing what they are capable of on offense. They both also struggled on the defensive side of the football forcing the total of 54.5 to open as the largest on the Week 2 NFL betting board. Buffalo has homefield advantage playing the first regular season NFL game inside new Highmark Stadium and is positioned as an early 4.5-point favorite on NFL Thursday Night Football this week.

NFL Thursday Night Football This Week

An inter conference clash between teams with Super Bowl aspirations takes the airwaves in Week 2 of NFL Thursday Night Football. The Lions survived their opener losing a 21-point lead to the Saints before winning in overtime 31-30 stopping a game-winning 2-point conversion attempt. The Bills, and in particular Josh Allen, exorcised some demons beating Houston 36-31. Buffalo has won the last five meetings between the clubs and is positioned as a 4.5-point NFL betting favorite to make it six straight.

Thursday Night NFL Football Game Preview

• NFL Thursday Night Football this week features an interconference matchup between the NFC’s Detroit Lions and the AFC’s Buffalo Bills on September 17, 2026.
• Kickoff is slated for 8:15 p.m. ET with the game broadcast on Amazon Prime Video.
• This will be the first regular season NFL game played in Buffalo’s new $2.1 billion Highmark Stadium, which seats more than 60,000 fans.

Key Storylines for This Week’s Matchup

• Two premier teams competing on NFL Thursday Night Football this week will take over once the game starts. However, leading up to kickoff the storyline will be the regular season debut of Buffalo’s brand new stadium. A raucous home crowd will create a hostile environment for the visiting Lions, who will have to manage the surroundings in their first road date.
• Detroit’s secondary was an area of concern entering last week’s game and the group allowed Tyler Shough to throw for 410 yards and three TDs. The Lions must patch the holes before facing Josh Allen.
• The Lions haven’t beaten Buffalo since the 2006 season, dropping the previous five matchups. If Detroit is to be considered among the elite Super Bowl contenders they must prove they can win big games on the road, and this one qualifies.

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Who Plays Thursday Night Football NFL?

Placed in different conferences when the Bills were absorbed by the NFL as part of the 1970 merger, the teams don’t have a long history. The Thursday night NFL football game between the Lions and Bills is just the 14th all-time meeting. Detroit will be the answer to a trivia question, though, as Buffalo’s first regular season opponent at the new Highmark Stadium. The Bills won the most recent meeting 48-42 during the 2023 season and have won five in a row over the Lions.

Team Matchup

• The Lions had a hard time containing Tyler Shough and the Saints last week and it’s not going to be easier against Josh Allen. The Bills integrated DJ Moore into the offense with five catches for 100 yards and a TD. Allen was 20 of 29 for 334 yards and two TDs against the stingy Texans and could have a bigger game against the Lions.
• The workload of Detroit’s Jahmyr Gibbs needs to be monitored so he’s not worn out by Thanksgiving. Gibbs rushed for 156 yards and two scores on 29 carries setting up the offense for play-action. The Lions are one of the best at that tactic and it only works if the ground game is a threat.
• Both teams need to shore up defensive shortcomings that were evident in Week 1. Detroit’s secondary was burned for more than 400 passing yards and the Bills surrendered nearly 400 total yards and 31 points with their new-look scheme.

Current Records and Recent Form

• Both teams won their opener in dramatic style. Detroit held on after nearly blowing a three-TD lead in the third quarter beating New Orleans, 31-30, in overtime. The Lions stopped a potential game-winning 2-point try after the Saints scored late in the extra session.
• Buffalo got a go-ahead TD pass from Josh Allen to Joshua Palmer with 96 seconds left to edge the Texans, 36-31. The win stopped a 6-game losing streak in Houston.
• The Bills take a five-game winning streak over the Lions into the contest, but all five games were decided by 6 points or less with a total of 15 points separating the teams.

Where Can I Watch Thursday Night NFL Football?

The Week 2 NFL Thursday Night Football game between the Lions and Bills will air exclusively on Amazon Prime Video as part of the streaming platforms contract with the NFL. Amazon Prime will broadcast every game that falls under the NFL Thursday Night Football umbrella.

TV and Streaming Information

• The Thursday night NFL football game will stream exclusively on Amazon Prime Video.
• If your local market team is playing on NFL Thursday Night Football the game will be broadcast on a local over-the-air television station in that team’s market.
• Starting in Week 2 every game under the Thursday Night Football umbrella will be broadcast directly through the Prime Video app.

Thursday Night Football Start Time

• Every game during the regular season under the NFL Thursday Night Football umbrella will have a start time of 5:15 p.m. PT / 8:15 p.m. ET.

NFL Thursday Night Football Odds and Best Bets

The Lions and Bills enter this short week matchup after pulling out dramatic victories in Week 1. Early NFL betting market action is trending toward the home team with Buffalo the home favorite opening their new stadium. After both teams reached the 30-point mark in their opener, NFL Thursday Night Football predictions are projecting a high-scoring affair. The NFL betting odds listed are current as of this writing.

Moneyline Odds

• Detroit Lions +192
• Buffalo Bills -223

Point Spread

• Detroit Lions +4.5 (-103)
• Buffalo Bills -4.5 (-113)

Game Total

• Over 54 (-104)
• Under 54 (-112)

NFL Thursday Night Football Predictions

Going off what we saw last week this game could have an outrageous amount of points scored. Both teams have been strong offensively for several years with the Bills led by former MVP Josh Allen and the Lions boasting a plethora of weapons on that side of the football. The NFL Thursday Night Football odds and best bets are backing the OVER of 54 points with the Lions getting the outright win.

Matchup Prediction

• Was Week 1 an aberration of is that the new normal in the NFL? We’ve seen trends toward more scoring and last week there was an abundance of points. On Thursday the team that is able to make stops and force turnovers has the advantage.
• The Lions surrendered 469 yards to the Saints, but they also came up with some big plays forcing three turnovers and recording five sacks. The Lions pitched a first half shutout before allowing 30 points in the second half and overtime.

Score Prediction

• Most analysts are backing a Buffalo win in their NFL Thursday Night Football predictions. We know they’re not always right just like last Thursday when the Rams were the choice. This is an exciting time for the Bills in their new stadium and the emotion will play a role allowing the Lions to take advantage.
• The total of 54 points will be surpassed in Detroit’s 31-27 victory.

Betting Prediction

• The Lions are looking to rebound from a forgettable last season when they finished 9-8 and missed the playoffs making this game against a Super Bowl contender a litmus test.
• Both teams will make adjustments defensively, but they’ll also continue to apply pressure on offense making the OVER a target in NFL Thursday Night Football predictions.
• If Week 1 and recent matchup history shows us anything it’s that the game is likely to be close. Toss in two of the NFL elite clubs and we could have an epic showdown.

NFL Thursday Night Football Bets to Consider

The top NFL Thursday Night Football bets to consider for the premier Week 2 contest between Detroit and Buffalo focus on offense after both teams had highly productive outputs in narrow opening day wins. The NFL betting line at the time of this writing had the total set at 54 points, the highest on the weekly board. 

Best Spread Bet

• Detroit possesses a balanced and efficient offense with playmakers all over the field. Backing the Lions and the points is a smart play in what should be a close game.

Best Total Bet

• Both teams looked to be in mid-season from offensively last week each scoring more than 30 points. However, the defenses failed to consistently stop opposing attacks making the OVER an attractive betting option.

Best Moneyline Bet

• According to some experts the best NFL Thursday Night Football bet on the moneyline is backing the Bills at their price. 
• Buffalo boasts an incredible home field advantage and fans will be out in force for the opening of the new stadium proving highly disruptive for the Lions. 
• Josh Allen accounted for four touchdowns last week and historically thrives in primetime matchups.

NFL Thursday Night Football Player Props

Many of the strongest NFL Thursday Night Football player prop targets are on the offensive side of the football after the Lions and Bills had productive games last week. The stars were shining with Jahmyr Gibbs and Amon-Ra St. Brown each scoring two TDs for the Lions while Josh Allen threw for two TDs and rushed for two more. 

Quarterback Props

• With the running game so effective, Jared Goff had only 206 passing yards last week. He did throw two TD passes and is a threat to pass in the red zone opening up the OVER on his total TD passes.
• It’s probably safe to back the OVER on any player prop involving Josh Allen. His dual threat ability will frustrate Detroit defenders giving him chances to find the end zone.

Running Back Props

• Jahmyr Gibbs is the key piece in Detroit’s backfield now and he carried the load rushing for 156 yards last week. Look for Gibbs to go OVER his low rushing yard total of 50.5.
• To negate Detroit’s pass rush the Bills will use James Cook for quick check downs helping him go OVER his receptions total of 2.5.

Receiver Props

• With Buffalo focusing on Amon-Ra St. Brown, look for tight end Sam LaPorta to be a bigger option in the passing game.
• DJ Moore was inserted flawlessly into the Bills’ game plan and had instant chemistry with Josh Allen. There’s a good chance he replicates his 100-yard receiving effort against a suspect Detroit secondary.

Key Factors for Thursday Night NFL Football Game Predictions

The key factors for NFL Thursday Night Football predictions for the high-stakes Week 2 matchup center around schematic and environmental factors. While the Lions and Bills were efficient on offense, they showed flaws defensively. And the opening of a new stadium in a primetime window guarantees a raucous crowd that could disrupt Detroit’s offensive rhythm and communication.

Short Week Rest and Injuries

• NFL Thursday Night Football games inherently limit preparation time and make it more difficult for the road team due to travel constraints. 
• Both teams escaped their season openers without any major injury concerns. Lions starting DB Avonte Maddox exited last week’s game with an arm injury but later returned.
• Buffalo’s Terrel Bernard and Cole Bishop briefly left the Houston game with minor ailments, but both were able to return later in the contest.

Home-Field Advantage

• Playing at home on NFL Thursday Night Football is an advantage in itself, but being one of the best home teams in the league makes it even more valuable.
• Over the previous five seasons the Bills won more than 81 percent of all their home games.
• There is an interesting dynamic with this contest being the first regular season NFL game in the history of new Highmark Stadium.

Matchup Trends

• This is actually a rare matchup that we’re seeing on NFL Thursday Night Football with the Lions and Bills meeting for just the 14th time.
• Buffalo leads the all-time series that started in 1972 winning eight of the 13 games with a tie. The Bills have won the last five matchups going 3-2 ATS with every game decided by six points or less.
• The teams last played in 2024 with the Bills earning a 48-42 decision. Jared Goff threw for 494 yards and 5 TDs in the losing effort. Josh Allen threw for 362 yards and accounted for four TDs.

NFL Thursday Night Football Betting Trends

NFL Thursday Night Football betting trends offer distinct historical patterns due to the game’s unique short-week setup that leaves teams less time to prepare. Understanding these trends and identifying specific team trends for the Lions at Bills showdown can help bettors spot value in certain betting lines.

Against the Spread Trends

• NFL betting line favorites historically win and cover the spread more frequently on Thursday’s compared to standard Sunday results.
• The compressed schedule makes it more difficult for underdog coaching staffs to implement a complex game plan needed for an upset.
• Cover rates often improve later in the season as teams start to forge an identity.

Over/Under Trends

• Games on short rest feature higher scoring volatility and totals tend to trend toward the UNDER as the season progresses.
• Oddsmakers adapt to the short week under factor which creates high-variance lines early in the season.

Head-to-Head Trends

• Detroit went OVER the total in 10 of 17 games last season and easily cashed the OVER last week. Buffalo hit the OVER last week and the teams defy the traditional narrative of a sluggish NFL Thursday Night Football game.
• Sitting as a 4.5-point favorite on the NFL betting line, the Bills struggled in this scenario last season going 4-7 ATS when favored by at least 4.5-points.