It's a tough week to gauge with injury uncertainty across the board, but here are my three favorite sides for Week 6 in the NFL.
I also played the Panthers, Saints and 49ers (although a little less bullish on San Francisco with the uncertainty surrounding Mac Jones and Ricky Pearsall being ruled out).
Let's get into my NFL Week 6 picks and predictions for Sunday, October 12.
NFL Week 6 Picks & Predictions
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Editor's Note: A parlay of these picks is not the author's formal recommendation. These NFL picks have value as straight bets.
Seahawks vs Jaguars
Seattle, unfortunately, didn't receive great news in the secondary with Riq Woolen, Devon Witherspoon and Julian Love all listed as doubtful, but it will get DeMarcus Lawrence back up front.
The defensive back injuries certainly hurt them, but it's not like this Jacksonville passing attack has lit the world on fire this season, ranking below average in both Success Rate and EPA.
On the other hand, the Seahawks' run defense continues to play at a top-five level, ranking third in EPA per Rush. That's critical against a Liam Coen offense in which everything starts with the ground game. I don't envision Jacksonville (which will be without its starting center) having much success in that department.
Even if Jags quarterback Trevor Lawrence does have a big day, there's no reason why Seattle can't match score for score with relative ease.
QB Sam Darnold is playing at an incredibly high level in Klint Kubiak's offense. Darnold ranks No. 1 in the league in EPA+CPOE, Adjusted EPA per Play and Success Rate. He's also absolutely shredded zone coverage, which he'll see plenty of on Sunday.
Jacksonville received good news with the return of defensive end Travon Walker, who will provide a massive boost to the pass rush, as Seattle will not simply be able to key in on Josh Hines-Allen.
However, the Jaguars defense likely has major turnover regression coming. Yes, they rank sixth in EPA per play and 16th in Success Rate, but those drop to 23rd and 18th without turnovers, respectively.
One season after finishing with a league-low nine takeaways, Jacksonville already has 14 in 2025 — four more than any other team in the league. That's not sustainable. For reference, while Jacksonville leads the league with a +8 turnover margin, Seattle sits at -1 through five games.
The Jags will also have to deal with a new secondary rotation on a short week after trading Tyson Campbell for Greg Newsome, who will walk into a drastically new scheme.
Trust the better offense to get it done on the road against a Jaguars team that is coming off a short week after an emotional upset win.
For what it's worth, Seahawks head coach Mike Macdonald has consistently had his teams ready to go on the road, where he is 9-1 SU with a 6-3-1 ATS record, including 5-1 against the closing number as an underdog.
Additionally, home Sunday favorites following an upset on Monday Night Football have gone just 20-29-1 ATS (40.8%) since 2003.
Pick: Seahawks +1.5
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Lions vs Chiefs
Everybody is now penciling the Lions into the Super Bowl after writing them off after a blowout loss to open the season in Green Bay. You gotta love the week-to-week take switch-ups in this league. I'm not sure I'm ready to crown them just yet.
Detroit has looked great during its four-game winning streak, but some context is needed. The Lions played two of the most injury-ravaged defenses in the league in Chicago and Baltimore, followed by wins over bottom-feeders Cleveland and Cincinnati, whose now-benched quarterbacks basically handed the game away on a silver platter.
Well, now the Lions have one of the most decimated defenses in the league on the back end, while the Chiefs come into this game at pretty much full strength.
Detroit will essentially be without its top four corners, with both safeties banged up as well. That's not great against a Chiefs offense that has found its mojo over the past two weeks with Xavier Worthy back in the mix and the emergence of Tyquan Thornton.
I had my doubts after the explosion against Baltimore, considering the state of that outfit, but K.C. followed that up last week with a 64% success rate — the single-highest clip of any team this season.
Detroit got away with its secondary injuries last week due to QB Jake Browning's incompetence, but this is a much different test (with even more injuries) against the best quarterback on the planet (Patrick Mahomes), who is now back to throwing downfield again.
Detroit usually plays plenty of man coverage, but will, in all likelihood, be forced into a much higher zone rate with its backup corners against one of the fastest wide receiver rooms in the league. That's not an ideal approach against Mahomes, who should have a field day on Sunday night.
The Lions will have success on the ground against a Chiefs defense that has struggled in that area, but they may be shorthanded along the offensive line with the status of stud left tackle Taylor Decker in doubt.
Kansas City also has an elite corner in Trent McDuffie, who is as capable as any in the league at trying to contain Amon-Ra St. Brown, regardless of whether he lines up outside or in the slot.
Ultimately, I'm a believer in this resurgent Chiefs offense that should have no issues moving the ball against a depleted Detroit secondary.
The complete desperation spot and some potential wet and windy conditions (which Lions QB Jared Goff doesn't thrive in) certainly don't hurt matters for Kansas City.
Pick: Chiefs -2.5
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Bills vs Falcons
We got a good one on Monday Night Football with the Falcons hosting a likely salty Bills bunch following their upset loss on Sunday Night Football.
I'm rolling with the home 'dog here.
While the bye week tends to get overrated under the new rules, it should help Atlanta get healthier in this case — specifically at wide receiver and with the return of No. 1 corner A.J. Terrell, who should provide a major boost for a corner group without great depth.
Not only do I see value in this number, but I also don't mind the matchup against a Buffalo squad that hasn't lived up to its rating over the past few weeks.
Following an improbable comeback win over the Ravens, the Bills destroyed the Jets (but who doesn't?). However, since that 2-0 start, they found themselves in wars at home against the Dolphins and Saints, then lost outright as a touchdown-plus favorite at home vs. the Patriots.
The 4-1 start looks nice on the surface, but this team isn't playing at an elite level at the moment, even though they're facing one of the league's easiest schedules, with four of their first five games at Orchard Park.
So, what has been the main culprit? It's the defense, specifically against the run — although the secondary has also struggled at times.
On the season, the Bills rank 28th in Rush EPA and 22nd in Rush Success Rate, which could spell trouble against Atlanta's run-heavy offense, led by Bijan Robinson. That should allow Michael Penix Jr. to hit some easy throws off play-action against the Bills' struggling backfield.
Penix also does a fantastic job of evading pressure behind a solid offensive line. That will negate the one primary strength of this Buffalo defense, which is getting to opposing quarterbacks. The Falcons can control the clock here and keep Josh Allen off the field.
When the Bills do have the ball, Allen will certainly have success (especially indoors, where he thrives), but this is a vastly improved Atlanta defense that is able to generate pressure as a result of its offseason additions.
There's no way to shut down Allen completely, but Atlanta's defense frequently uses a high rate of zone coverage and blitz, which has historically been the best approach to slowing down No. 17.
Pick: Falcons +4.5
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Anytime Touchdown Parlay
Trey McBride Anytime TD + Ashton Jeanty Anytime TD
