With both the Buffalo Bills and Philadelphia Eagles taking a loss last week, no undefeated teams remain in the NFL and we're only going into Week 6. That's the first time that's happened in the league since 2014, but this once-in-a-decade happenstance makes things that much more interesting. Teams like the Detroit Lions are heating back up, teams like the Baltimore Ravens are decisively not, and there are sleepers such as the New England Patriots emerging (especially after being the ones to hand the Bills their first loss). And that's all on my mind going into making NFL Week 6 picks and predictions.
The Lions are in a particularly interesting position going into NFL Week 6. They've won four straight and have done so in dominant fashion since opening the year with a demoralizing loss to the rival Packers. Now, they'll be in primetime as they go on the road to face a Kansas City Chiefs team that's under .500 but is favored in this matchup at home. New England is another team getting hot as well, now winning two straight games that includes the upset victory over rival Buffalo. With Drake Maye turning a corner, the Pats look like a real threat.
I've been preaching about trying to figure out a strange season in the NFL for a while now, and my NFL picks have definitely reflected that, especially coming off of a losing week. It does, however, feel like we might have a better read going forward, and here's to hoping that we can reflect that with a winning week of NFL Week 6 picks with predictions straight-up and against the spread for all 15 games on the slate, including another London game and a Monday night doubleheader.
2025 NFL Picks Straight-Up Record: 47-31 (Last Week: 6-8) | ATS Record: 33-45 (Last Week: 6-8)
Note: All lines are courtesy of FanDuel Sportsbook. Game odds refresh periodically and are subject to change. If you or someone you know has a gambling problem and wants help, call 1-800-GAMBLER.
NFL Week 6 predictions: Picks straight-up and ATS for every game
NFL Week 6 Matchup | Straight-Up Pick | ATS Pick |
|---|---|---|
Eagles at Giants (TNF) | Eagles | Giants +7.5 |
Broncos at Jets (London) | Broncos | Broncos -7 |
Browns at Steelers | Steelers | Browns +5.5 |
Chargers at Dolphins | Chargers | Chargers -4.5 |
Patriots at Saints | Patriots | Patriots -3.5 |
Seahawks at Jaguars | Jaguars | Jaguars -1.5 |
Cardinals at Colts | Colts | Cardinals +6.5 |
Rams at Ravens | Rams | Rams -7.5 |
Cowboys at Panthers | Cowboys | Cowboys -3 |
Titans at Raiders | Titans | Titans +5.5 |
49ers at Buccaneers | Buccaneers | Buccaneers -3 |
Bengals at Packers | Packers | Packers -14.5 |
Lions at Chiefs (SNF) | Lions | Lions +2.5 |
Bills at Falcons (MNF) | Bills | Bills -4.5 |
Bears at Commanders (MNF) | Bears | Bears +4.5 |
Teams on bye in Week 6: Houston Texans, Minnesota Vikings.
We're starting the week off on Thursday Night Football with a mild hot take, which is that the Giants can cover at home against the Eagles. Jaxson Dart might have his work cut out for him offensively, but the defense should be able to slow down an inconsistent Philly offense enough to keep this one semi-close.
Moving into the weekend, though, there's a ton of intrigue with Joe Flacco potentially debuting for the Bengals as more than two-touchdown underdogs t the Packers, the aforementione Lions-Chiefs matchup, Bears-Commanders in a great Monday night clash, and sneakily the 49ers taking on the Buccaneers in Tampa in a battle of potential NFC contenders.
Toughest NFL Week 6 prediction to make
Detroit Lions (+2.5) at Kansas City Chiefs
Looking at the slate before I even took a single gander at the lines, I suspected that Detroit would be the favorite, even on the road at Arrowhead. The fact that the Lions are, instead, just shy of a field goal underdog on the road had me scratching my head. That ultimately led to me second-guessing backing Dan Campbell's team in this matchup, but I'm still going to end up rolling with the Lions both straight-up and against the spread in this matchup.
Kansas City has actually started to show signs of breaking out of their early-season funk offensively, but the Lions are a different beast. Even if the Chiefs still continue their upward trajectory behind Patrick Mahomes, I don't see the balance with the run game yet, which the Lions can exploit with Aidian Hutchinson and Co., while I also don't know that Steve Spagnuolo has the horses, particularly in the trenches, to stop the Detroit's offense with the way Jared Goff and Company are cruising right now.
The fact that the Lions are underdogs combined with the respect you simply have to maintain for the Chiefs makes me wary of this pick, but I'll stick to my guns when it comes to Detroit.
Easiest NFL Week 6 pick on the board
New England Patriots (-3.5) at New Orleans Saints
Maybe it'll be foolish to say that this is an easy pick in Week 6, especially because Spencer Rattler and the Saints have not been pushovers in recent weeks by any stretch, even beating the Giants quite handily last week. The fact that they're at home could also be complicating this prediction as well. And yet, my gut tells me that what we saw from Drake Maye and the Patriots on Sunday night against Buffalo wasn't a fluke.
Point blank, I think the Patriots are leveling up before our eyes and that the market may not have fully caught up to that. It can't go unnoticed how much better the defense is playing now that Christian Gonzalez and several others are back and healthy, which went somewhat unnoticed because of Maye in the win over the Bills. Throw in the fact that the Saints won't be able to test the Patriots young offensive line meaningfully, Maye has the chance to pick them apart.
There's a chance that I end up eating crow on this one, but I think the Patriots are a playoff team that simply aren't being recognized as such yet. That gives us an edge against a group like the Saints.
The pick that probably has you scratching your head
Tennessee Titans (+5.5) at Las Vegas Raiders
Let's be abundantly clear that I don't think either the Titans or Raiders are really any kind of good right now. If that's actually the truth, though, then why in the world would one of these teams be a 5.5-point favorite in this matchup? And from where I'm sitting, it makes even less sense that the Las Vegas team that's been inept offensively behind Chip Kelly and Geno Smith is the one favored by that margin when the Titans, although extremely flawed, have at least shown some hope with Cam Ward getting his feet wet.
While there's always a chance that the veterans on the Raiders, and specifically Maxx Crosby in this matchup, could show up and outclass these young, highly imperfect Titans, I'm not willing to say that's even enough for them to cover a 5.5-point spread in this game. The Titans have enough firepower on both sides of the ball to keep this one close. And for good measure, my lack of faith in what I've seen from the Raiders ultimately led to me sticking my neck out and thinking the Titans actually pick up the win outright.
In a world where I'm being asked to trust a Raiders team that's been an abject failure to this point, I'm going to take the alternative 99-of-100 times.