Lions vs. Bills Prediction, Odds, Spread, Injuries, Trends for NFL Week 2

Thursday Night Football in Week 2 of the 2026 NFL season features a marquee matchup between the Buffalo Bills and Detroit Lions, two teams with Super Bowl expectations.

Both of these teams had wild finishes in Week 1 of the season, though the Bills’ win over the Houston Texans was much more impressive than Detroit’s victory over the New Orleans Saints.

Josh Allen led the Bills to a comeback win over Houston, throwing for over 300 yards while combining for four scores. The win was a huge one for a Bills team that entered Week 1 as just a 1.5-point road favorite.

The Lions nearly blew a major lead against the Saints, who forced overtime and had a chance to win with a two-point conversion. Detroit’s offense came through with a touchdown in the extra period, but Jared Goff and Co. stalled a few times, including late in the game where they settled for a field goal, eventually allowing the Saints back in.

That won’t work against Allen and this vaunted Buffalo offense, and oddsmakers have set the Bills as favorites at home on a short week.

Here’s a look at the odds, a player to watch, injuries, betting trends and a game prediction for this Thursday Night Football showdown.

Lions vs. Bills Odds, Spread and Total for NFL Week 2

Odds via DraftKings Sportsbook

Spread

Lions +3 (-105)
Bills -3 (-115)

Moneyline

Lions: +140
Bills: -166

Total

52.5 (Over -105/Under -115)

Lions vs. Bills How to Watch

Date: Thursday, Sept. 17
Time: 8:15 p.m. EST
Venue: Highmark Stadium
How to Watch (TV): Prime Video
Lions record:
Bills record:

Lions vs. Bills Injury Reports

Lions Injury Report

Christian Mahogany – questionable
Kerby Joseph – PUP
Brian Branch – PUP
Cade Mays – IR
Isiah Pacheco – IR

Bills Injury Report

Ty Johnson – questionable
Jedrick Wills Jr. – questionable
Tyrell Shavers – PUP

Lions vs. Bills Betting Trends

The Lions are 0-1 against the spread this season.
The Bills are 1-0 against the spread this season.
The Bills are 1-0 when favored this season.
The OVER hit in Week 1 for both of these teams.
The Bills were 9-10 against the spread last season.
The Lions were 8-9 against the spread last season.

Lions vs. Bills Key Player to Watch

Josh Allen, Quarterback, Buffalo Bills

Josh Allen showed why he’s the MVP favorite in Week 1, throwing for 334 yards and two scores while rushing for 23 yards and two more touchdowns to beat the Texans.

Allen led a late fourth quarter drive to take the lead, ripping an absolute dime to Josh Palmer on a deep post to give Buffalo a 36-31 lead that held up as the final. Allen’s performance was yet another display of how he can carry an offense, and he spread the ball around to several receivers with Dalton Kincaid (five catches, 130 yards) and DJ Moore (five catches, 100 yards) leading the way.

There’s a chance Allen has another huge day in Week 2 against a Detroit secondary that is a little banged up. Detroit allowed over 400 passing yards to Tyler Shough in the overtime win in Week 1, and Shough isn’t nearly as dynamic of an offensive player as Allen.

Lions vs. Bills Prediction and Pick

The Lions have a fairly easy schedule in the 2026 season – outside of this matchup – but I did not come away impressed with this team in Week 1.

With safeties Kerby Joseph and Brian Branch out, the Lions were routinely torched by the Saints and Shough, allowing nearly 200 receiving yards for Chris Olave. Things will not get any easier with Allen, James Cook and this Buffalo attack coming off a strong showing against a Houston defense that was easily the best in the NFL in 2025.

Buffalo was able to cover the spread against Houston, and it came up with a key stop in the final seconds, stripping C.J. Stroud on a third-and-goal play.

Detroit’s offense can compete with just about anyone when it’s rolling, but I entered the season skeptical of this secondary after it was in the bottom half of the league in EPA/Pass in 2025 with Branch and Joseph in the lineup for a lot of it.

Buffalo should have an elite home crowd in this primetime matchup, and I will gladly bet on Allen and Co. in what may be an offense-first battle.

Pick: Bills -3 (-115 at DraftKings)

Odds refresh periodically and are subject to change.

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