The Buffalo Bills and coach Joe Brady make their Highmark Stadium regular-season debut when they battle the NFC North-contending Detroit Lions on 'Thursday Night Football' to get the Week 2 NFL schedule underway. The Bills opened the season with an impressive 36-31 win over the Houston Texans in Week 1, while the Lions held off the New Orleans Saints 31-30 in overtime. Detroit (1-0), which finished fourth in the NFC North, was 9-8 in 2025.
Buffalo (1-0), which was second in the AFC East, went 12-5. Detroit will be without two starting offensive linemen, including 2026 first rounder Blake Miller. Claim the latest Polymarket promo code CBSSPORTS to get a $50 bonus after $10 in trades: Kickoff is set for 8:15 p.m.
Bills odds have Buffalo as 5.5-point favorites, a 2.5-point increase from opening at Buffalo -3. Meanwhile, the over/under for total points scored is 54.5. Buffalo is 10-10 ATS since the start of last season, with Detroit at 8-10.
Before making any Lions vs. Bills picks or 2026 NFL Week 2 predictions, be sure to see what the SportsLine projection model has to say. The model, which simulates every NFL game 10,000 times, is up well over $7,000 for $100 players on betting sites on top-rated NFL picks since its inception.
The model enters Week 2 of the 2026 NFL season on a 53-39 run on top-rated picks dating back to 2024. Anybody following its picks at NFL betting sites could have seen strong returns. Now, the model has zoned in on Lions vs.
You can head to SportsLine now to see its picks. Here are several NFL odds and betting lines for Bills vs. Lions: New to sports trading?
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