NFL Week 6 Best Bets (Predictions for Lions vs. Chiefs, Seahawks vs. Jaguars on Sunday)

The SI Betting team breaks down their favorite bets for Week 6 of the 2025 NFL season, including a pick for the Detroit Lions-Kansas City Chiefs matchup.

The Detroit Lions are a solid underdog bet in Week 6. / Lon Horwedel-Imagn Images

Week 6 in the NFL is upon us, and it’s a perfect time for some best bets for Sunday’s action as the SI Betting team aims to roll some positive momentum into this week’s edition for NFL Best Bets.

NFL betting insider Iain MacMillan made a perfect call in Week 5, taking the Denver Broncos as 4.5-point underdogs against the Philadelphia Eagles, and Denver ended up winning the game outright!

However, with every great pick comes a bad beat, and Peter Dewey may have suffered the worst one of the season last week. The Arizona Cardinals blew a 21-6 lead over the Tennessee Titans thanks to a comedy of errors (Emari Demercado’s goal-line fumble and a fumbled interception for a touchdown), losing not only against the spread, but the entire game.

With that terrible loss behind us, can we go 2-0 in Week 6? 

This week, Dewey and MacMillan are targeting a pair of small underdogs to cover the spread – and potentially win outright. 

Let’s dive into the breakdowns for each best bet in Week 6 of the 2025 season.

NFL Best Bets for Week 6

Odds via FanDuel Sportsbook.

• Seattle Seahawks +1.5 (-115) vs. Jacksonville Jaguars – Iain MacMillan
• Detroit Lions +2.5 (-110) vs. Kansas City Chiefs – Peter Dewey

Seattle Seahawks +1.5 (-115) vs. Jacksonville Jaguars – Iain MacMillan

The advanced metrics love this Seattle Seahawks team this season. 

Heading into Week 6, they rank second in the NFL in DVOA and Sam Darnold has quietly been having one of the most impressive seasons amongst NFL quarterbacks, ranking first in both adjusted EPA per play and completion percentage over expected. 

The Seahawks coaching staff has also been calling near-perfect games as well. Now, they get to take on a Jacksonville Jaguars team that, while 4-1, is flawed in some aspects, especially offensively. 

Trevor Lawrence has been in the bottom 10 in the league in most metrics and the amount of turnovers the Jaguars' defense has been causing simply isn't sustainable moving forward. 

I'll back the Seahawks on the road.

Detroit Lions +2.5 (-110) vs. Kansas City Chiefs – Peter Dewey

Patrick Mahomes has dominated in his career as an underdog, but I think the Lions are the team to bet in this matchup.

Detroit has really turned things around after a rough Week 1 loss to the Green Bay Packers, and it ranks fourth in EPA/Play on both offense and defense. The Lions have run for the sixth-most yards in the NFL, and they should end up destroying this Kansas City defense on the ground in Week 6 – which has allowed 4.8 yards per carry and ranks 29th in the NFL in EPA/Rush. 

Yes, the Chiefs have won two of their last three games, but they have struggled against superior competition, going 0-3 against the Jaguars (4-1), Philadelphia Eagles (4-1) and Los Angeles Chargers (3-2). 

On top of that, the Chiefs are 0-3 in one-score games, and this spread suggests that they’ll play another close game in Week 6.

Harrison Butker has also struggled for Kansas City, missing five kicks this season and he made a crucial mistake in Week 5, kicking his final kickoff out of bounds to give the Jaguars great field position on their game-winning drive.

Detroit has covered the spread in every game since Week 1, and the team’s offense is humming at the moment, ranking No. 1 in points scored and seventh in yards per play.

With Rashee Rice still suspended, I’m not sure that Kansas City has the offensive firepower to keep up in this game, especially if it continues to struggle stopping the run.

I’ll take the points with Detroit, as it’s one of my favorite upset targets in Week 6.

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Odds refresh periodically and are subject to change.

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