NFL Upset Predictions and Picks for Week 5 (Will 49ers Upset Seahawks in NFC West Showdown?)

Peter Dewey cashed in on his upset pick in Week 4, correctly predicting the Atlanta Falcons to beat the New Orleans Saints on Monday Night Football.

We move on to Week 5 and four of our writers have an upset pick they love for this weekend's action. Let's dive into them.

Gilberto Manzano, NFL Staff Writer
Mike Kadlick, NFL Senior News Writer: 9-7 (-2.35 units)
Iain MacMillan, Senior Editor, Betting
Peter Dewey, Associate Managing Editor, Betting

All odds listed are via DraftKings Sportsbook

Gilberto Manzano Week 5 Upset Pick

Green Bay Packers (+114) vs. Chicago Bears

This might be Matt LaFleur’s Super Bowl after the embarrassing postseason collapse against his arch rival Ben Johnson. LaFleur might not admit it, but I’m sure there’s extra motivation with all the trash talk the Bears did after the wild-card victory. And it’s somewhat of an insult that the Packers are home dogs to a team that might not have its starting quarterback available. Caleb Williams is nursing a hamstring injury. Yes, Jordan Love has taken a beating this year with a poor offensive line, but the Bears aren’t known for their pass rush. Give me Green Bay to end my losing streak. Eventually, I’ll get an upset pick correct here.

Mike Kadlick Week 5 Upset Pick

Los Angeles Chargers (+154) vs. Denver Broncos

This is one of those classic “make the pick and look away” type of bets for me. While the Chargers have shown no life through the first month of the season, the Broncos haven’t exactly shown their 2025 AFC No. 1 seed-earning prowess either. Denver is 0–2 on the road this year and has yet to score more than 14 points while away from Mile High Stadium.

As such, I’m going with my gut here and saying that the Chargers—in their first game back at home since Week 2—will somehow find a way to notch their first win of the season, quieting the Justin Herbert–Jim Harbaugh–Mike McDaniels doubters. At least for one week.

Peter Dewey Week 5 Upset Pick

Cleveland Browns (+105) vs. New York Jets

I can’t believe I’m betting on the Cleveland Browns and Deshaun Watson in 2026, but they’ve been impressive during this 3-1 start, and I think they should be favored on the road in this matchup with the New York Jets.

New York couldn’t slow down Tyson Bagent and the Chicago Bears in Week 4, allowing them to possess the ball for nearly 43 minutes in a loss. Since they beat the Tennessee Titans in Week 1, the Jets have dropped three games in a row, and their offense is extremely banged up.

Breece Hall, Omar Cooper Jr., Mason Taylor, and Adonai Mitchell all missed Week 4, and Geno Smith simply isn’t good enough to elevate a shaky supporting cast.

The Browns outrank the Jets in defensive success rate (New York is 29th) this season, and Watson has looked more like the quarterback he was in Houston than he ever has in Cleveland. This young Browns team is intriguing in the AFC North if he keeps playing well. Watson is 14th in success rate amongst quarterbacks with at least 100 plays in 2026.

Iain MacMillan Week 5 Upset Pick

San Francisco 49ers (+130) vs. Seattle Seahawks

In my opinion, the San Francisco 49ers have been the best team in the NFL through the first four weeks. They lead the league in DVOA, Net Yards per Play, EPA per Play, and success rate. Brock Purdy has also been one of the best quarterbacks in the NFL, leading the league in several metrics, including adjusted EPA per play.

The Seahawks are also one of the best teams in the NFL, but in what I think is largely a coin flip game, I'm going to back the underdog at +130 odds.

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