Joe Osborne
• Senior Betting Analyst
16+ years betting experience
Updated:
Sep 15, 2026 , 10:31 PM ET
• 4 min read
The Lions are 4.5-point underdogs on Thursday Night Football in Buffalo, and our early Lions vs. Bills predictions lean toward the visitors covering.
Photo By – Reuters Connect. Detroit Lions running back Jahmyr Gibbs (0) carries the ball against the New Orleans Saints
The Buffalo Bills are 4.5-point favorites as they open their new stadium on Thursday Night Football against the Detroit Lions, who have enough offensive firepower to spoil the party.
My early Lions vs Bills predictions back the visitors to make things competitive, while a shootout is the highlight of my NFL picks.
Both teams survived Week 1 nail-biters, and Week 2 is poised to kick off similarly on Thursday, Sept. 17.
Lions vs Bills predictions
For help understanding Kalshi probabilities, see our odds calculator.
| Pick |  Probability |
|---|---|
| Lions +4.5 | 52% |
| Over 53.5 | 50% |
Percentages courtesy of Kalshi, one of the best prediction market apps.
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Early Lions vs Bills spread pick: Lions +4.5
Kalshi probability: 52%
The Detroit Lions have the offense to go shot for shot with the Buffalo Bills, especially after the Bills surrendered 31 points to an average-at-best Texans attack.
Plenty will be made of the Lions traveling on a short week after overtime, but that narrative feels overblown. It’s Week 2. These players are fresh, and overtime added just two possessions, so that won’t be a deciding factor.
What could be a factor, however, is the scare the Lions had after almost blowing a 21-0 lead. Expect that to light a fire under Detroit for their first primetime game of the season.
There’s also a question worth asking: What would this spread be had Buffalo lost Sunday? Without a dropped interception late, that easily could have been the case. The Bills escaped, but that doesn’t erase their defensive concerns. Give me Detroit and the 4.5 points in a battle of Super Bowl hopefuls.
The Lions are 5-1 ATS in their last six games as an underdog of more than three points.
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Early Lions vs Bills total pick: Over 53.5
Kalshi probability: 50%
Over 53.5 is my top prediction after these offenses combined to score 67 points in Week 1. Buffalo dropped 36 on one of the league’s best defenses behind a ridiculous 7.9 yards per play.
Detroit took its foot off the gas after building a 21-0 lead midway through the third quarter, but it has another gear. Following an underwhelming opener last season, the Lions scored 34-plus in four straight games.
Both defenses raised red flags. Buffalo allowed 31 points to a Texans team that struggled to score consistently last season, while Detroit let New Orleans move up and down the field with ease throughout the second half and overtime.
Expect the Bills to light up the scoreboard in their new stadium, but their defense should give Detroit plenty of opportunities to join the fun.
It’s also worth noting that these teams combined for 90 points in Buffalo’s 48-42 win in 2024.
Lions vs Bills odds
For help understanding Kalshi probabilities, see our odds calculator.
- Lions vs Bills spread: Bills -4.5
- Lions vs Bills moneyline: Lions 34%, Bills 66%
- Lions vs Bills Over/Under: 53.5
How to watch Lions vs Bills
- Date: Thursday, Sept. 17, 2026, 8:15 p.m. ET
- City: Orchard Park, N.Y.
- Venue: Highmark Stadium
- TV: Prime Video
Odds are correct at the time of publishing and are subject to change.
Not intended for use in MA.
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