Bills vs. Lions predictions, odds, time: Week 2 'Thursday Night Football' picks by proven model

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. Claim the latest Polymarket promo code CBSSPORTS to get a $50 bonus after $10 in trades:

Kickoff is set for 8:15 p.m. ET from Buffalo. The latest Lions vs. Bills odds have Buffalo as 4.5-point favorites, while the over/under for total points scored is 53.5. 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. Bills. You can head to SportsLine now to see its picks. Here are several NFL odds and betting lines for Bills vs. Lions:

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Top Lions vs. Bills predictions

After 10,000 simulations of Lions vs. Bills, the model is going Over 53.5 points at betting apps. Both teams had no problem putting up points in Week 1. Detroit running back Jahmyr Gibbs was explosive against the Saints, carrying 29 times for 156 yards and two touchdowns. He also caught five passes for 30 yards. Quarterback Jared Goff was efficient, completing 26 of 39 passes for 206 yards and two touchdowns.

Josh Allen, the 2024 NFL MVP, looked back to his old form in the season opener, completing 20 of 29 passes for 334 yards and two touchdowns. He also rushed six times for 23 yards and two scores. Tight end Dalton Kincaid caught five of six passes for 130 yards, including three explosive plays of 20 or more yards. The Over has hit in seven of the Lions' last 10 games, and in six of the last 10 Bills games. The model projects 58 combined points, giving value to the Over in 57% of simulations. See which team to back at SportsLine. 

How to make 'Thursday Night Football' picks

In addition to going Over, the model also says one side of the spread is hitting in more than 50% of simulations. See what it is at SportsLine.

Who covers in Lions vs. Bills, and which side of the spread hits more than 50% of the time? Visit SportsLine now to see which side of the Lions vs. Bills spread you need to jump, all from the model that's on a 53-39 run on top-rated picks since 2024, and find out.