NFL Upset Predictions and Picks for Week 17 (Eagles Are Live to Upset Bills on Sunday)

Iain MacMillan | 1 Hour Ago

The Eagles are +118 underdogs against the Bills in NFL Week 17 action. / Sports Illustrated

The SI Team did a great job with their upset picks in Week 16. Matt Verderame cashed on the Tennessee Titans to beat the Kansas City Chiefs at +144, and Peter Dewey correctly predicted the Carolina Panthers at +130 against the Tampa Bay Buccaneers.

It's time to look ahead to Week 17, and with plenty of upset opportunities available, two of our three panelists are targeting the Eagles to take down the Bills in a potential Super Bowl preview. Let's take a look.

Odds via FanDuel Sportsbook

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

Matt Verderame Week 17 Upset Pick

Houston Texans +112 vs. Los Angeles Chargers

The Chargers are playing really good football, coming off impressive wins against the Eagles, Chiefs and Cowboys. Now they come home on a short week to face the Texans, who are riding a seven-game winning streak on the back of a ferocious defense.

The concern here is whether the backup tackles of Los Angeles can block the combination of Will Anderson Jr. and Danielle Hunter off the edge. The two have combined for 24.5 sacks, while Justin Herbert has been sacked 49 times, fewer than only than Cam Ward and Geno Smith. If the Chargers can’t hold up on the edges, it could be a long day.

Iain MacMillan Week 17 Upset Pick

Philadelphia Eagles +118 vs. Buffalo Bills

The Buffalo Bills escaped Cleveland with a win in Week 16, but it was further proof that they're a team with more issues than their record indicates. Their biggest issue is their defense, specifically their complete inability to stop the run. The Bills have allowed a blistering 5.4 yards per carry, the second most in the NFL. They also rank 31st in opponent rush EPA and 27th in opponent rush success rate. Now, they have to take on an Eagles team that is seemingly hitting their stride of late, especially in the run game.

The Eagles have averaged 4.9 yards per carry over their last three games, which has served as a beautiful compliment to a defensive unit that has been one of the best in the league in the second half of the season. Not only are the Eagles a great team to invest in based on how they're playing of late, but the stylistic matchup in this game sways heavily in Philadelphia's favor.

Peter Dewey Week 17 Upset Pick

Philadelphia Eagles +118 vs. Buffalo Bills

The Philadelphia Eagles have already clinched the NFC East this season, but I think they're a live underdog against a Buffalo team that has been a little shaky at times in the 2025 season, including last week when it nearly blew a game against the Cleveland Browns.

Buffalo ranks 31st in the league in yards per carry allowed (5.4) this season, and that should be a major concern against a Philadelphia offense that loves to run the ball – led by Saquon Barkley, who has 332 rushing yards over his last three games.

This season, the Bills are just 5-8 against the spread when favored, and I think these teams are pretty even entering Sunday’s matchup. Philly, which hasn’t been an underdog all season until this point, has outscored its last two opponents (Washington and Las Vegas) by a tally of 60-18. Don’t be shocked if Philly pulls off the upset in Buffalo.

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