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Lions vs. Bills Prediction: Week 2 Early Pick & Opening Odds

Our early Lions vs. Bills prediction for Week 2 includes our best bet, opening odds, and the latest line movement ahead of Thursday's matchup.

Liam Fox

Last Updated: September 14, 2026 9:43 AM EDT • 2 minute read

Pictured: Buffalo Bills wide receiver DJ Moore celebrates as we break down our Lions vs. Bills early prediction. Photo by Thomas Shea via Imagn Images.

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With the Buffalo Bills opening a brand-new stadium on Thursday Night Football against the Detroit Lions, my Lions vs. Bills early prediction explains why you should bet the total now based on the opening odds.

Thursday's kickoff is set for 8:15 p.m. ET from new Highmark Stadium in Orchard Park, N.Y., with the Bills currently priced as a 3.5-point home betting favorite. The game will air on Prime Video.

🏈 Early Lions vs. Bills prediction: Week 2

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Over 52.5 (-118 via FanDuel)

This could be one of the highest-scoring games of the entire season, given the firepower on both offenses. It would have to be a sky-high total to scare me away from taking the Over for Thursday's prime-time matchup.

Both the Bills' and Lions' season openers totaled Over 60 points on Sunday. Beyond the scoring success of the Josh Allen- and Jared Goff-led offenses, each team's defense barely held on against subpar opposing passing attacks (Texans and Saints). Buffalo's new Highmark Stadium will be christened with a shootout.

FanDuel is the only one of our best sports betting sites still offering the opening total of 52.5. Grab the Over on that number while you can, but I'd still wager at the 53.5-point total available everywhere else.

📡 SBR Edge - Expect a barn burner in Buffalo

Detroit and Buffalo's Week 1 contests featured an average of 64 points.

📊 Lions vs. Bills odds & line movement: Week 2

See the latest NFL odds.

Lions vs. Bills opening odds

Moneyline: Lions +134 | Bills -165
Spread: Lions +3 (-110) | Bills -3 (-110)
Over/Under: Over 52.5 (-110) | Under 52.5 (-110)

Lions vs. Bills line movement

The point spread has moved to Bills -3.5 after Week 1, and I expect that to move further in Buffalo's favor playing at home. As for the total, it's up to 53.5 at most sportsbooks. Already the highest projected total of Week 2, this number will likely continue upward as the majority of bets are being wagered on the Over. If you're like me, you'll want to bet the Over now before that happens.

📺 How to watch Lions vs. Bills: NFL Week 2

Date: Thursday, Sept. 17
Kickoff: 8:15 p.m. ET
Location: Highmark Stadium (Orchard Park, N.Y.)
Streaming: Prime Video

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Written by:
Liam Fox

Liam Fox is a Publishing Editor for Sportsbook Review. Liam spent the past seven-plus years in the sports media industry building his NFL experience and contributing at some of North America's top outlets. His work has appeared on Sportsnet, Forbes, and Complex. He was previously an editor for nearly four years at theScore, specializing in NFL coverage. His career highlights include asking Patrick Mahomes a question at Super Bowl LV media day and shedding light on the champion Philadelphia Eagles' use of analytics through an in-depth interview with their lead data analyst. A graduate of Carleton University's Bachelor of Journalism program, you can usually find Liam writing about sports, watching sports, or playing sports.