NFL Upset Predictions and Picks for Week 10 (Bet Giants to Take Down Bears in Chicago)

Iain MacMillan | Nov 6, 2025

The Giants are +162 underdogs against the Bears in Week 10 of the NFL season. / Ian Maule/Getty Images, Rich Barnes-Imagn Images

We are officially through the halfway point of the 2025 NFL season, and while favorites have had a big year, the SI panel has managed to correctly call a few upsets each week. In Week 9, Conor Orr correctly predicted the Cardinals to take down the Cowboys, and Matt Verderame nailed the Steelers beating the Colts.

The SI team has their upset picks locked in for Week 10, so let's take a look at them and see if we can cash in on a few underdog winners again!

Odds via FanDuel Sportsbook

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

Gilberto Manzano Week 10 Upset Pick

San Francisco 49ers (+188) vs. Los Angeles Rams

The 49ers haven’t gotten as much attention as the Rams and Seahawks—two teams that San Francisco has already beaten this season. This team is constantly being overlooked because of several injuries to key players, but San Francisco has had L.A.’s number over the years and still has many star players on the offensive side. I’m expecting monster performances from Christian McCaffrey and Trent Williams.

Clare Brennan Week 10 Upset Pick

New England Patriots (+120) at Tampa Bay Buccaneers

The Patriots will get their biggest test since their Oct. 5 showdown with the Bills when they travel to Tampa to take on the Buccaneers. Coming off a bye, Baker Mayfield & Co. will be rejuvenated after the beleaguered squad got some much-needed rest. Sunday’s matchup will be a tall task for the Pats, with New England’s O-line needing to protect Drake Maye against the blitz-heavy Bucs and help establish the run game. But if Mike Vrabel’s side can do that, it may just pull out the road victory, with New England currently riding a six-game win streak.

Matt Verderame Week 10 Upset Pick

Pittsburgh Steelers (+126) at Los Angeles Chargers

For the second consecutive week, I’m riding with the Steelers. Pittsburgh took care of business last weekend, beating the Colts 27–17 to maintain a two-game lead in the AFC North. This week, Mike Tomlin’s team gets to play against a Chargers team without star tackles Joe Alt and Rashawn Slater. 

While Pittsburgh’s defense ranks towards the bottom in many categories, including points and yards allowed, the Steelers should get pressure with T.J. Watt, Alex Highsmith, Nate Herbig, and Cam Heyward going against a front that allowed six sacks to the Jeffrey Simmons-less Titans in Week 9.

Iain MacMillan Week 10 Upset Pick

New York Giants (+162) vs. Chicago Bears

The Bears continue to find ways to win games against bad teams, but their average scoring margin of -1.5 shows they may not be as good as their record indicates. If you're a believer in the advanced metric called DVOA, you'd be interested to find out that these two teams rank right next to each other at 22nd and 23rd.

At the end of the day, in what is set as a coin flip game, I have more faith in Jaxson Dart, who has shown all the signs of being a baller that can drag his team to victories they may not deserve otherwise. I can't say the same thing about Williams. Dart ranks 16th in the NFL in Expected Points Added + Completion Percentage Over Expected, while Williams ranks just 23rd.

Peter Dewey Week 10 Upset Pick

Philadelphia Eagles (+116) vs. Green Bay Packers

Despite all the worries and questions about the Philadelphia Eagles this season, they’re in first place in the NFC and coming off a bye that should help them get both Saquon Barkley and A.J. Brown healthy.

I cannot trust the Green Bay Packers, who have had terrible losses to Cleveland and Carolina, playing plenty of shaky halves of football this season. They won’t be able to have a letdown against this Philly team that is top-10 in the league in EPA/Play on offense. 

Green Bay has some great numbers on defense (it’s No. 2 in the league in yards per play allowed), but it has not put together a lot of complete games in the 2025 season. 

Nick Sirianni’s Eagles are a perfect 4-0 after the bye since he took over as the team’s head coach, and I expect that streak to continue on Monday night.

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Odds refresh periodically and are subject to change.

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