NFL Upset Predictions and Picks for Week 5 (Will the Buccaneers Upset the Seahawks?)

Iain MacMillan | Oct 2, 2025

Buccaneers are underdogs against the Seahawks in Week 5. / Baker: Cliff Welch/Icon Sportswire via Getty Images, Darnold: Steph Chambers/Getty Images

Favorites are still winning at a high clip in the NFL, but we saw at least a couple of upsets last week. Both the New York Giants and Dallas Cowboys won as 6.5-point underdogs in Week 4.

When it comes to the SI Betting panel, Gilberto Manzano correctly called the Atlanta Falcons pulling off the upset against the Washington Commanders, and Matt Verderame correctly predicted the Kansas City Chiefs taking down the Baltimore Ravens.

It's time to move on to Week 5. The SI Team has their upset picks locked in, so let's dive into them.

• Clare Brennan, Associate Editor
• Gilberto Manzano, NFL Staff Writer
• Matt Verderame, NFL Staff Writer
• Iain MacMillan, Senior Editor, Betting
• Peter Dewey, Associate Managing Editor

Odds via FanDuel Sportsbook

Clare Brennan Week 5 Upset Pick

Carolina Panthers (-102) vs. Miami Dolphins

Which Panthers team will show up on Sunday? After shutting out the Falcons in Week 3, Carolina was trounced by the Patriots in Week 4. Facing off against one of the worst run defenses in the league, with the Dolphins allowing 5.1 YPC on the season, Bryce Young and the Panthers will have an opportunity to get the ground game going, which could be a tall task for a team averaging 100.3 rushing yards per game. 

Tua Tagovailoa will get his opportunities as well, with the Panthers’ defense allowing Drake Maye and the Patriots to hang up 42 points in New England. With Tyreek Hill out for the season, Jaylen Waddle will be Tagovailoa’s primary target and will get plenty of looks against an inconsistent Panthers defense. 

Both teams are struggling mightily this year, but with Miami on the road during a short week, maybe this is a chance for Carolina to pounce and bounce back from an embarrassing and demoralizing loss.

Gilberto Manzano Week 5 Upset Pick

Cleveland Browns (+162) vs. Minnesota Vikings

Don’t be fooled by the blowout losses against the Lions and Ravens. This game is ripe for another Browns upset victory, similar to the Week 3 win in Green Bay. The Browns don’t have enough offense to hang with the elite teams. But they do have a stout defense that can frustrate the non-star QBs. 

Whether it’s against Carson Wentz or J.J. McCarthy, it won’t matter much because both signal-callers are bound to make mistakes vs. Myles Garrett & Co. Also, this is the second game of a two-game stint overseas for the Vikings. 

Matt Verderame Week 5 Upset Pick

Tampa Bay Buccaneers (+152) vs. Seattle Seahawks

The Buccaneers are coming off their first loss of the season, and although they’re both banged up and having to fly cross-country to play this game, they remain the better team. 

Seattle is a good squad, but there are clear issues. The Seahawks needed every second to beat the Cardinals, and have already lost to the 49ers at home. Speaking of being at home, the Seahawks have been awful at Qwest Field under coach Mike Macdonald recently, with a straight-up record of 2–6 in their last eight games.

While Sam Darnold has been solid with 905 passing yards and five touchdowns against two interceptions, Seattle is struggling to run at 3.6 yards per carry. Against Tampa Bay, the Seahawks face the league’s second-best run defense by YPC at 3.3. It’s tough to win as a one-dimensional offense.

Iain MacMillan Week 5 Upset Pick

New England Patriots (+360) vs. Buffalo Bills

It's been a while since I've made this bold of an upset pick, but I see a lot of issues with this Bills team. Let's remember how weak their schedule has been since Week 1. Their last three games have come against the Jets, Dolphins, and Saints. Despite that, they rank only seventh in Net Yards per Play (+0.9), and their defense ranks 22nd in opponent EPA per play, 17th in opponent success rate, and 22nd in defensive DVOA. To have those numbers while playing three of the worst teams in the NFL is a real problem.

Meanwhile, Drake Maye has had a fantastic start to his sophomore season. He's sixth amongst starting quarterbacks in EPA+CPOE composite and adjusted EPA per play. Their defense has had some problems of its own, but they rank right around the same as the Bills in several categories.

This has all the makings of an offensive shootout, and if the Bills aren't careful, the Patriots have a chance of pulling off an AFC East upset. I'll take a shot on New England as a big-time underdog.

Peter Dewey Week 5 Upset Pick

Tampa Bay Buccaneers (+152) via Seattle Seahawks

Seattle has gotten off to a strong start in the 2025 season, but I’m not sold on it being an NFC West contender because it has wins over Pittsburgh, New Orleans, and Arizona (on a short week).

The Seahawks are a top-10 team in EPA/Play on defense, but they are in the middle of the pack (15th in EPA/Play) on offense.

Meanwhile, the Tampa Bay Buccaneers are 11th in the NFL in both offensive and defensive EPA, and they’re starting to get healthier with Chris Godwin returning to the lineup in Week 4. Even though Tampa is coming off a loss to the Philadelphia Eagles, it held the defending champs in check on offense in the second half. 

I think this is a much easier matchup for Tampa Bay, which has started the season 3-1 despite being down key players on the offensive side of the ball. I love the Bucs getting three points in this game, but I’ll also take them to win outright on Sunday.

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