Prime Video’s 2026 NFL Thursday Night Football opener could be one of Week 2's best matchups as the Detroit Lions face the Buffalo Bills at 8:15 p.m. ET tonight. The Bills enter as 4.5-point home favorites, with a slate-high 54.5-point over/under — up from the opening number of 52.5.
Both teams are coming off Week 1 shootouts, as the Lions escaped with a 31-30 win over the New Orleans Saints, while the Bills got a late score to outlast the Houston Texans 36-31.
Needless to say, we should expect some fireworks on Thursday night. This will also be the opening game at Highmark Stadium, Buffalo’s new home venue. Which of these two playoff contenders emerges from this clash 2-0?
Below, we’ll break down our Lions vs. Bills prediction and picks for Week 2’s Thursday Night Football game tonight, including the spread, over/under, and top player picks for PrizePicks.
With Bills WR DJ Moore's receiving yards on promo tonight — discounted to 34.5 from 62.5 yards — it's even easier to cash in on your NFL picks on PrizePicks!
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Lions vs. Bills Prediction, Spread, Over/Under for Thursday Night Football Week 2
Last season, the Lions averaged both the fifth-most points per game (28.3) and fifth-most yards per game (373.2).
However, advanced metrics reflected an offense that wasn’t quite as explosive and consistent as those raw numbers would suggest. Detroit ranked ninth in EPA/play (0.071) and just 12th in success rate (45.0%), according to RBSDM.
This was after ranking third (0.155) and first (49.6%), respectively, in those categories the season prior when Ben Johnson was still the offensive coordinator. Those 2024 Lions led the league in PPG (33.2), too.
As a result, Detroit moved on from OC John Morton and brought in former Arizona Cardinals OC Drew Petzing to call plays. Early 2026 returns have to be considered a mixed bag following Week 1.
While the Lions put up 31 points, they ultimately finished with a lackluster -0.027 EPA/play and were middle of the pack in success rate (45.5%).
Injuries to the offensive line are undoubtedly the biggest concern coming into Thursday. C Cade Mays is already on IR, while RT Blake Miller and LG Christian Mahogany have both been ruled out this week.
Last year on defense, the Lions finished a respectable 15th in EPA/play (0.012) and 11th in success rate (42.6%) but faded down the stretch due in part to injuries.
The defense is also already undermanned to open the year, as the secondary is without both S Brian Branch and S Kerby Joseph. That likely contributed to Detroit blowing a 21-0 lead against New Orleans, ultimately needing a failed two-point conversion in OT to escape with the 31-30 victory.
The pass rush should still be a strength, though, after the team finished tied for fourth in sacks last season (49). In Week 1, the Lions racked up 5 sacks and finished seventh in pass rush win rate (60%), per ESPN.
In 2025, the Bills’ attack finished third in EPA/play (0.145) and second in success rate (48.8%).
Buffalo picked up right where it left off in Week 1, dropping 36 points on the Texans, a team that’s supposed to have one of the NFL’s top defenses. Unsurprisingly, it sure looks like this will be a lethal attack with new head coach Joe Brady now having full reign following Sean McDermott’s firing this offseason.
Defensively last year, Buffalo ranked 13th in EPA/play (-0.007) and 12th in success rate (43.0%). However, they were shredded by opposing RBs, coughing up the fifth-most rushing yards per game (136.2) while allowing the second-most EPA/rush (0.049).
Much like the Lions, the Bills’ defense didn’t exactly get off on the right foot in Week 1 after allowing 31 points to the Texans and giving up the league’s ninth-highest success rate (48.1%).
They also gave up the ninth-most EPA/rush (0.030), which doesn’t bode well for them with RB Jahmyr Gibbs coming to town. That being said, Detroit's injuries could help Buffalo contain the star halfback.
Lions vs. Bills Spread, Over/Under – Thursday, September 17
The Bills enter Thursday’s game as 4.5-point home favorites against the Lions, returning a 1.38x payout on PrizePicks if they win outright.
Play the Lions vs. Bills spread or over/under on PrizePicks!
Team Picks data is live at the time of writing and is subject to change.
Lions vs. Bills Prediction on Spread for Thursday Night Football – 9/17/26
Here are the key stats and trends behind our Lions vs. Bills prediction on the spread for Thursday, September 17.
- The Lions enter Thursday effectively missing three starters on their offensive line and both starting safeties. CB D.J. Reed (foot) is also questionable.
- The Bills produced an absurd 0.300 EPA/play in Week 1 against the Texans. In 2025, Houston had an elite defense that ranked second in EPA/play (-0.108) and second in success rate (39.5%).
- Buffalo’s offensive line finished last week ranked first in pass block win rate (71%).
- QB Josh Allen had a stellar day at the office last week, piling up 334 passing yards and 2 TDs while also adding 23 yards and another 2 TDs on the ground.
- Last week, the Lions picked off Saints QB Tyler Shough twice but also allowed him to throw for 410 yards and 3 TDs in a comeback attempt that fell just short.
- Detroit's -0.027 EPA/play on offense against New Orleans ranked just 19th in Week 1.
Make your Lions vs. Bills picks now for Thursday’s NFL game.
Lions vs. Bills Picks, Player Stats for TNF on PrizePicks: 9/17/26
Here are the top Lions vs. Bills picks to target on Thursday, September 17. Today’s NFL picks for PrizePicks include Dalton Kincaid, Jahmyr Gibbs, and Amon-Ra St. Brown.
Bills WR DJ Moore vs. Lions: 34.5 Receiving Yards (Promo)
- PrizePicks is running a special Taco Tuesday Flash Sale on DJ Moore's receiving yards — down to 34.5 yards from 62.5, his standard projection.
- Moore caught 5 passes on 8 targets for 100 yards and a TD in his Bills debut.
- The Bills' new WR1 topped the discounted projection in one catch last week on his 43-yard touchdown.
- Dating back to 2024, Moore has reached more than 35+ yards in 16 straight games where he gets 6+ targets, including postseason games.
- Moore averaged 71 yards in those 6+ target games — more than double this discounted projection.
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Bills TE Dalton Kincaid vs. Lions: 52.5 Receiving Yards
- In Week 1, Kincaid caught 5 of 6 targets for 130 receiving yards. That was good for a 21.4% target share, per SumerSports. He’ll now face a banged-up Lions secondary.
- Kincaid played 72.4% of the offensive snaps, per Pro Football Reference. In 2025, he never exceeded 55.0% in 12 games. There are reportedly no snap restrictions for him this year.
- According to PlayerProfiler, Kincaid had a 66.7% route participation rate. He was at only 51.1% in 2025.
- Despite his modest usage in 2025, Kincaid produced 2.70 yards per route run, the highest mark among TEs.
Add Dalton Kincaid + Bills to cover the spread to your PrizePicks lineup now.
Lions RB Jahmyr Gibbs vs. Bills: 4 Receptions
- In 2025, Gibbs averaged 4.5 receptions per game while playing 67.1% of the snaps in a split backfield with RB David Montgomery. His 74.0% snap rate in Week 1 would’ve been his third-highest clip last season.
- Last week, Gibbs caught all 5 targets for 30 receiving yards in a game where the Lions never trailed and were leading by at least a touchdown for the majority of it.
- Between the possibility of falling into a negative game script in a hostile road environment and the Lions missing multiple offensive linemen, Gibbs might see a bump in his passing game usage.
- In Week 1, QB Jared Goff logged 39 pass attempts. A whopping 36 of those throws targeted WR Amon-Ra St. Brown, WR Jameson Williams, TE Sam LaPorta, and Gibbs. No one else on the team saw more than a single target.
Add Jahmyr Gibbs + Bills to cover the spread to your PrizePicks lineup now.
Lions WR Amon-Ra St. Brown vs. Bills: 7.5 Receptions
- St. Brown led Detroit in receptions (10) and targets (14) against Houston with a hefty 35.9% target share. His route participation rate was at 95.1% in Week 1.
- Excluding an injury-shortened Week 13 last year, the receiver averaged 10.7 targets across his 16 healthy weeks.
- Dating back to last season, St. Brown had 8+ receptions in four of his last five games.
- The Lions allowed a 49.2% dropback success rate to the Saints last week.
Add Amon-Ra St. Brown + Bills to cover the spread to your PrizePicks lineup now.
Make Lions vs. Bills Picks on PrizePicks
We should see a fun Thursday Night Football game between the Detroit Lions and Buffalo Bills in Week 2. Which team will win this potential shootout?
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