Detroit Lions vs. Buffalo Bills: Experts release early Week 2 predictions [2026]

The Detroit Lions and Buffalo Bills will meet in Week 2 of the NFL season at Highmark Stadium on Thursday, September 17, 2026, starting at 8:15 PM ET.

Early simulations from Dimers' trusted NFL model favor the Bills as the most likely winner of this cross-conference meeting.

For updates all week long, including best bets, player prop projections and touchdown probabilities, check out our interactive Lions vs. Bills predictions page.

Detroit vs. Buffalo early predictions

Leveraging trusted machine learning and analysis, we have simulated the Lions vs. Bills game 10,000 times as part of our NFL predictions coverage. Here are the latest insights:

• Straight up win probabilities: Lions 36.8%, Bills 63.2%
• Predicted final score: Lions 24-27 Bills
• Spread: Lions (+3.5) 50.0%, Bills (-3.5) 50.0%
• Total points (53.5): Over 46.6%, Under 53.4%

As of September 14, 2026, these Lions-Bills numbers and predictions reflect the latest data and insights available.

Lions vs. Bills Week 2 details

Thursday's game between the Bills and Lions at Highmark Stadium is scheduled for September 17, 2026.

• Who: Detroit Lions vs. Buffalo Bills
• Date: Thursday, September 17, 2026
• Time: 8:15 PM ET/5:15PM PT
• Venue: Highmark Stadium

Lions vs. Bills opening odds

We've researched the best betting odds across America for this Week 2 game, which are listed here:

• Spread: Lions +3.5 (+108), Bills -3.5 (-109)
• Moneyline: Lions +186, Bills -185
• Total: Over/Under 53.5 (+106/-108)

Odds may continue to move—track live changes via our NFL odds page.

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Conclusion

We predict the Bills, with a 63.2% win probability, will likely beat the Lions in Week 2 of the NFL season. Dimers.com will provide full game coverage closer to kickoff, so stay tuned for updates.

Enhanced by AI and automation, this article delivers quick, accurate insights on the Lions vs. Bills matchup, with human oversight maintaining high editorial quality. Our predictions are based on the latest data to help you make informed decisions. For additional resources and advice on responsible gambling, please call 1-800-GAMBLER.

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