Playoff contenders look to stay perfect on the season when the Detroit Lions battle the Buffalo Bills in a key interconference Week 2 matchup on 'Thursday Night Football' as Buffalo officially opens up its new Highmark Stadium. Detroit is coming off a 31-30 overtime win over the New Orleans Saints, while Buffalo held off the Houston Texans 36-31 on Sunday. The Lions are looking for their fifth consecutive winning season under coach Dan Campbell. The Bills, meanwhile, are looking to post their eighth winning season in a row and first under coach Joe Brady. Claim the latest Polymarket promo code CBSSPORTS to get a $50 bonus after $10 in trades:
Kickoff is at 8:15 p.m. ET from New Highmark Stadium in Orchard Park, N.Y. The latest Lions vs. Bills odds have Buffalo as a 4.5-point favorite, while the over/under for total points scored is 54.5, the highest on the Week 2 NFL odds board. Before making any Lions vs. Bills picks, or 'Thursday Night Football' predictions, be sure to see what Larry Hartstein has to say.
A former lead writer for Covers and The Linemakers, Hartstein combines a vast network of Vegas sources with an analytical approach he honed working for Pro Football Focus. He is coming off a 2025 NFL season in which he went 50-37 ATS (57.5%), putting him at 643-555 ATS all time. For NFL Office Pool players, Hartstein picked every game straight-up the past two seasons and nailed nearly 70 percent of those picks on NFL betting sites. He also enters this season on a 22-11-1 roll on his last 34 picks involving the Lions, returning $966 to $100 players. Anyone following his picks on betting sites could have seen huge returns.
Now, Hartstein has zeroed in on Lions vs. Bills. You can head to SportsLine now to see his picks. Here are several NFL odds and betting lines for Bills vs. Lions:
Lions vs. Bills spread
Bills -4.5
Lions vs. Bills over/under
53.5 points
Lions vs. Bills money line
Bills -230, Lions +190
Lions vs. Bills picks
Lions vs. Bills streaming
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Top Lions vs. Bills predictions
Hartstein is leaning Over 54.5 combined points for over/under betting at betting apps. Both teams have high-powered offenses, while both defenses struggled in Week 1. Jahmyr Gibbs helped lead the Lions' attack, rushing for 156 yards and two touchdowns on 29 carries against New Orleans. Wide receiver Amon-Ra St. Brown caught 10 passes for 67 yards and two scores. Josh Allen, meanwhile, threw for 334 yards and two touchdowns for the Bills.
"The Lions' defense, which remains without safeties Kerby Joseph and Brian Branch, was on the field for a whopping 86 plays in Sunday's 31-30 overtime win over New Orleans," Hartstein said. "Now that tired unit must try to stop Josh Allen and co. in the Bills' home opener. These are the same Bills who shredded what many believe to be the NFL's top defense in a 36-31 win over Houston." See which team to back at SportsLine.
How to make Lions vs. Bills picks
Hartstein also has found a crucial X-factor that makes one side of the spread a must-back. See what it is at SportsLine.
Who wins Lions vs. Bills on Thursday Night Football, and what X-factor makes one side of the spread hit hard? Visit SportsLine now to see which side of the Lions vs. Bills spread you need to jump, all from the expert who has returned $966 to $100 players over his last 34 Detroit Lions picks, and find out.
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