The Buffalo Bills open their new Highmark Stadium on Thursday, September 17, hosting the Detroit Lions at 8:15 p.m. ET.
My Lions vs. Bills prediction expects more fireworks with a selection on the total leading my NFL picks for the Week 2 edition of Thursday Night Football, with the Bills currently -4.5-point favorites.
TOP PICK
Lions vs Bills prediction: Over 53.5
These offenses combined for 67 points in Week 1, and there’s plenty of reason to expect another shootout. The Buffalo Bills dropped 36 on Houston’s formidable defense behind a ridiculous 7.9 yards per play, while the Detroit Lions scored 31 despite taking their foot off the gas after building a 21-0 lead midway through the third quarter.
The defensive red flags are equally encouraging. Buffalo surrendered 31 points to an average-at-best Texans offense, while Detroit let New Orleans march up and down the field with ease after halftime.
The Bills were a wagon at home last year and should want to put on a show in their debut at their new stadium. Detroit's high-flying offense can go shot for shot with them and should be on their A-game after almost blowing a 21-0 lead in Week 1.
For what it's worth, their 2024 meeting produced a 48-42 Buffalo win, and we need considerably less scoring to cash this one.
COVERS INTEL: The Bills have scored 30 or more points in 13 of their last 17 regular-season home games.
Lions vs Bills combo
Both offenses crossed the 30-point mark in their openers, while both defenses struggled to get stops. Detroit has enough firepower to keep Buffalo aggressive throughout the night, giving us a strong setup for sustained scoring from both sides.
Josh Allen threw for 334 yards on just 29 attempts against Houston and now faces a defense that surrendered 410 passing yards to Tyler Shough. With Detroit capable of keeping pace, Buffalo should need Allen throwing well into the fourth quarter.
Dalton Kincaid opened with five catches on six targets for 130 yards against Houston. Detroit allowed Juwan Johnson and Noah Fant to combine for 87 receiving yards, making 50-plus an appealing target without needing another explosive performance from Buffalo’s tight end.
Lions vs Bills combo
- Over 53.5
- Josh Allen 250+ Passing Yards
- Dalton Kincaid 50+ Receiving Yards
TOP PICK
Lions vs Bills touchdown scorer: DJ Moore
At 35%, DJ Moore offers fair value for his role among this game’s top offensive playmakers.
He drew eight targets in his Buffalo debut, turning them into 100 yards and a touchdown. Now he gets a Lions secondary that allowed Tyler Shough to throw for 410 yards and three scores.
With Buffalo expected to score plenty, Moore has the involvement and big-play ability to deserve serious consideration at this price.
- Top picks: 1-0, +1.00 units
- Combos: 0-1, -1.00 units
Lions vs Bills odds
For help understanding probabilities, see our odds calculator.
- Spread: Lions +4.5 | Bills -4.5
- Over/Under: Over 53.5 (52%) | Under 53.5 (48%)
- Moneyline: Lions 33% | Bills 67%
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Lions vs Bills weather
The forecast calls for temperatures near 69°F at kickoff with mostly cloudy skies and light winds, though showers earlier Thursday make rain timing worth monitoring.
Check out our NFL weather page for up-to-date info on every matchup.
Lions vs Bills trend to know
The Lions have gone Over in seven of their last nine games. Find more NFL betting trends for Lions vs. Bills.
How to watch Lions vs Bills
| Location | Highmark Stadium, Orchard Park, N.Y. |
| Date | Thursday, Sept. 17, 2026 |
| Kickoff | 8:20 p.m. ET |
| TV | Prime Video |
Lions vs Bills latest injuries
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