NFL Week 5 picks and predictions, straight-up and ATS: Chiefs, Colts getting back on track

Anyone who thought they had football figured out within the first month of the 2025 season probably doesn't feel that way going into NFL Week 5 now. If you were writing the death certificate for the Kansas City Chiefs, think again as they now go on the road for a huge AFC showdown with the Jacksonville Jaguars. Or if you thought the Daniel Jones-led Indianapolis Colts were the surprise juggernaut of the season, they came back to Earth already. With that and much more, that makes our NFL Week 5 picks that much more difficult.

We'll talk more about this, but this isn't exactly a banner week for the NFL in terms of the high-profile matchups we've been treated to. That doesn't mean that there won't be upsets, big surprises, and a ton of intrigue for contenders either trying to right the ship, get back on track, or keep things rolling, however. And we certainly need to get things rolling with our picks and predictions right now.

I'm not going to lie to y'all, we need to get hot. We took a bath last week against the spread, and I really have no one to blame but myself. Luckily, we still have 14 more weeks of NFL action to accomplish just that, and it starts with our NFL Week 5 picks with predictions for every game straight-up and against the spread.

2025 NFL Picks Straight-Up Record: 41-23 (Last Week: 9-7) | ATS Record: 27-37 (Last Week: 4-12)

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NFL Week 5 predictions: Picks straight-up and ATS for every game

Teams on bye in Week 5: Atlanta Falcons, Chicago Bears, Green Bay Packers, Pittsburgh Steelers.

There aren't necessarily the same marquee matchups that we've been treated to in recent weeks, but Week 5 still has a ton to offer. The aforementioned Chiefs-Jags game on Monday night should be a great one, the Bucs traveling across the country to face the Seahawks could be must-see TV, Broncos-Eagles could be ugly in all the intriguing ways, and even Giants-Saints has the second game for Dart we already talked about.

One thing to note, though, is that weeks like NFL Week 5 are the one wherein things seem to always get a little off-kilter. So if you're thinking that there might be some upsets or at least some unexpectedly close games, I can't blame you for thinking that way.

Toughest NFL Week 5 prediction to make

Chiefs (-3) at Jaguars

On the one hand, you have to like what you saw from the Chiefs on Sunday in a dominant victory over the Ravens. On the other, things seem to be, at least for now, crumbling a bit in Baltimore. That's a tricky combination in itself, but then you throw in the fact that the Jaguars are coming off of their best showing of the year to date in a win over the 49ers, and that further complicates matters — especially with Patrick Mahomes and Co. being in Jacksonville for this matchup.

The deciding factor in making this pick, however, wasn't based on Mahomes, though I do believe that the Chiefs will continue to look on the upswing when it comes to that side of the ball. Instead, it's about the Steve Spagnuolo defense that is also coming into form and the advantage I see that could give Kansas City against Liam Coen's offense. Make no mistake, I think the Jags hit a home run hiring Coen and his future is bright, but the experience of Spags and the way he can disrupt Trevor Lawrence could swing the game their way.

As always when it comes to the toughest pick of the week, this is far from my most confident prediction, but I do think the Chiefs can get ahead and win by more than the field goal when it's all said and done.

Easiest NFL Week 5 pick on the board

Lions (-10.5) at Bengals

While I understand that Detroit is on the road in a game that would be quite easy for the Lions to overlook, has anyone watched the Bengals lately? I wouldn't blame you if you did something better than watch them cosplay as a doormat on Monday Night Football this past week against the Broncos, but holy moly is it ugly right now in Cincinnati.

Even after bringing back Trey Hendrickson, all the Bengals accomplished was ensuring the defense would just be regular levels of bad as opposed to catastrophically awful. Since the Joe Burrow injury, though, the Jake Browning-led offense has been a disaster. Now that the Lions are starting to show the signs of clicking on all cylinders, I'm not even sure they need to be entirely locked in for this matchup to be able to pull away by more than two touchdowns on Sunday.

The pick that probably has you scratching your head

Vikings at Browns (+3.5)

With reports indicating that Browns head coach Kevin Stefanski is on the cusp of making the change from Joe Flacco to rookie Dillon Gabriel at quarterback, that could be worrisome for Cleveland. After all, not only are there the general nerves of a rookie making his first NFL start, but he'll have to do so abroad with this being a London game on Sunday morning. For good measure, he'll also be up against a Brian Flores defense.

But while I'm taking Flores' defense and the Vikings to win the game outright, I'm still going to take the Browns with three and a hook as underdogs in this matchup. That starts with Cleveland's defense, which has been legitimately one of the best units in the league this season, including against even better offenses such as the Packers. Now, they get to take on a Minnesota offense currently led by Carson Wentz and looking pedestrian at best.

Then we have Gabriel and, while I might not be his biggest fan, it's not hyperbolic to say that it can only get but so much worse for the Browns offensively at this point. I actually think we see a slight uptick thanks to some smart scheming from Kevin Stefanski, and Cleveland is ultimately able to keep it close, even if they aren't able to put a notch in the win column.