Best NFL Picks and Predictions Today (How to Bet Lions vs. Bills on Thursday Night Football in NFL Week 2)

Thursday Night Football in the 2026 season is off to an insane start.

After the NFL treated us to a San Francisco 49ers vs. Los Angeles Rams battle in Week 1, it returns with two potential Super Bowl contenders in the Buffalo Bills and Detroit Lions in Week 2.

Buffalo is playing the first game at its new stadium in this matchup, and it’s coming off an impressive road win over the Houston Texans in Week 1. Josh Allen combined for four scores in that game, throwing for 334 yards in the process. He had two 100-yard receivers as well in Dalton Kincaid and D.J. Moore.

Now, Allen has a chance to light up a short-handed Detroit secondary that allowed over 400 passing yards in an overtime win over Tyler Shough and the New Orleans Saints. The Lions’ offense was solid in Week 1 (31 points), but Detroit needed a stop on a 2-point conversion in overtime to secure the win.

So, it is facing an uphill battle as a road dog against one of the best teams in the AFC.

All week long the SI Betting team has been breaking down game picks, props, anytime touchdown scorer selections and more for this primetime matchup.

Here’s a look at some of our favorites for the Detroit Lions vs. Buffalo Bills showdown on Thursday night.

Best NFL Picks and Predictions for Lions vs. Bills

Odds via DraftKings Sportsbook

Detroit Lions +4.5 (-108) vs. Buffalo Bills – Iain MacMillan
Josh Allen OVER 250.5 Passing Yards (-111) – Peter Dewey
Sam LaPorta Anytime TD (+205) – Peter Dewey
Dalton Kincaid Anytime TD (+180) – Peter Dewey

Detroit Lions +4.5 (-108) vs. Buffalo Bills – Iain MacMillan

Earlier this week, SI Betting’s senior editor Iain MacMillan shared his best bet for this game in his Road to 272 column – where he bets on every game, every week – and he’s taking the points with the Detroit:

As tempting as it is to back the Bills after how both teams looked in the opening week, I have to do my best not to overreact to a one-game sample size and stick to my belief that the Lions are one of the best teams in the NFL. Their metrics were elite last season, but injuries and poor variance led to them missing the playoffs.

There's no denying that Josh Allen is once again going to be an MVP candidate, but let's not overlook the fact that their defense allowed the Texans to rack up yards and points against them last week. Their defensive roster is completely different from a year ago, so I didn't know what to expect from them this season, but ranking 19th in opponent EPA per play and 22nd in opponent success rate isn't a good start.

Josh Allen OVER 250.5 Passing Yards (-111) – Peter Dewey

Could we see yet another big game through the air from Allen?

The Bills quarterback torched the Houston Texans in Week 2, throwing for 334 yards and two scores. Houston was the No. 1 defense in EPA/Play in the 2025 season, yet Allen not only had a big game through the air, but he had two 100-yard receivers (DJ Moore and Dalton Kincaid) in the win.

Now, he takes on a Lions secondary that is down starting safeties Brian Branch and Kerby Joseph to begin this season. Detroit allowed 410 passing yards to Tyler Shough in Week 1, and a lot of those came in the second half with the Saints making a huge comeback.

Allen may not throw the ball over 50 times like Shough did, but this Buffalo offensive is capable of creating a ton of explosive plays.

Last season, Allen only averaged 215.8 passing yards per game, so there is some risk when it comes to this prop. Still, with Moore in the fold, I think Buffalo is well-equipped to attack a short-handed Lions secondary.

Sam LaPorta Anytime TD (+205) – Peter Dewey

Detroit Lions tight end Sam LaPorta received eight looks in Detroit’s season opener, catching five passes for 48 yards. While he didn’t find the end zone, I think there’s value in taking the star tight end at north of 2/1 to score.

The Bills gave up 274 passing yards and two scores to CJ Stroud and the Houston Texans in Week 1, and the Lions should be able to attack this defense through the air on Thursday night.

Jared Goff has looked to Amon-Ra St. Brown as his top target in the red zone, but LaPorta is a matchup nightmare with his size and mobility on the outside. Plus, the Bills (19th in EPA/Pass) don’t exactly have an elite secondary this season.

It’s also worth noting that LaPorta played 62 snaps (80.5 percent) in Detroit’s Week 1 win. He should be heavily involved in Week 2.

Dalton Kincaid Anytime TD (+180) – Peter Dewey

I’m all about the tight ends in this Week 2 clash.

Buffalo’s Dalton Kincaid was a first-round pick a few years ago, and he’s become an important part of the passing attack in Joe Brady’s offense.

Against Houston in Week 1, Kincaid finished with five catches (on six targets) for 130 yards, ripping off multiple huge gains. He didn’t find the end zone, but the Bills star had five scores in just 12 games in 2025.

This is a great matchup for Kincaid, as Detroit couldn’t guard New Orleans tight end Juwan Johnson late in Sunday’s game, allowing him to finish with three grabs for 54 yards and a score.

After spending most of the 2025 season playing less than 50 percent of the team’s snaps, Kincaid was out there for 72.4 percent of the offensive plays in Week 1. He’s a terrific target at this price against a Detroit defense that allowed 410 passing yards in its season opener.

Odds refresh periodically and are subject to change.

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