Lions vs. Bills Prediction: Week 2 Odds, Picks, Best Bet & Betting Splits (Sept. 17)

Our Lions vs. Bills prediction for Week 2 breaks down our best bet, projected final score, and the latest odds for Thursday Night Football.
Bills quarterback Josh Allen (17) rolls out as we break down our Lions vs. Bills prediction.
Pictured: Bills quarterback Josh Allen (17) rolls out as we break down our Lions vs. Bills prediction. Photo by Ron Chenoy / Imagn Images.
Enjoying SBR content? Add us as a preferred source on your Google account Add as a preferred source on Google

Two Super Bowl contenders collide at the new Highmark Stadium on Thursday Night Football, and I’m backing Josh Allen and the Bills in my Lions vs. Bills prediction.

Detroit escaped with a narrow Week 1 win over the Saints, but its performance left plenty to be desired. Buffalo, meanwhile, looked much sharper in its season opener. That contrast is reflected in the market, as the Bills are listed as a 4.5-point betting favorite, with kickoff in Orchard Park, N.Y., set for 8:15 p.m. ET (Prime Video).


🏈 Lions vs. Bills picks & predictions

See all of our experts' NFL picks for Week 2 based on the latest NFL odds.

Pick Bet size
BIlls -4.5 (-110 via BetMGM) 1 unit
Over 54.5 (-112 via bet365) 0.5 units

Total wagered: 1.5 units | Max profit: +1.36 units


💰 Lions vs. Bills prediction & best bet

Bills -4.5 (-110)

The Bills erupted for 36 points against a Houston Texans team that had the second-best defensive DVOA last season.

In the process, Allen got a gigantic monkey off his back in beating the Texans for the first time.

He’ll enter Thursday’s tilt brimming with confidence, especially as he faces a Lions secondary that was ripped apart in the second half at home against the New Orleans Saints.

Tyler Shough racked up 410 passing yards and three TDs in the 31-30 defeat.

Other than escaping with the win and Jahmyr Gibbs’ sensational performance, there wasn’t much to like about the Lions' Week 1 win.

📡 SBR Edge

Allen is 10-1 in September as a home betting favorite and 7-0 in the previous seven games. It’s also opening night for the new Highmark Stadium.

Lions secondary reeling entering TNF

The Lions’ top two safeties, Brian Branch and Kerby Joseph, will miss at least the first four games. And their absence in Week 1 was more noticeable than Dan Campbell’s second-half rage. 

Detroit has another injury concern heading into TNF, with starting cornerback DJ Reed sustaining a foot injury. 

He’s limited in practice and will likely be a game-time decision. Even with Reed, the Lions' secondary was leakier in Week 1 than a collection of open manholes, with the Saints’ Chris Olave posting a career-high 182 receiving yards on 10 receptions, representing another prime example.

Score prediction: Bills 31, Lions 24


📊 Lions vs. Bills odds

See the latest NFL odds for every Week 2 matchup.

Lions vs. Bills opening odds

  • Moneyline: Lions +140 | Bills -165
  • Spread: Lions +3 (-115) | Bills -3 (-105)
  • Over/Under: Over 52.5 (-115) | Under 52.5 (-105)

🎟️ Lions vs. Bills betting splits

Betting insights via BetMGM.

Team / bet type Odds Bet % Handle %
Lions
⚪ Moneyline +190 40% 24%
⚪ Spread +5.5 42% 36%
⚪ Total o55 62% 74%
Bills
🔴 Moneyline -235 60% 76%
🔴 Spread -5.5 58% 64%
🔴 Total u55 38% 26%

📺 How to watch Lions vs. Bills: Week 2

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

📃 Affiliate disclosure

Sportsbook Review may receive a commission if you sign up through our links. Not intended for use in MA. Bonuses not applicable in Ontario. 21+ only. (Gambling problem? Call 1-800-GAMBLER)