NFL Upset Predictions and Picks for Week 2 (Bengals, Giants, Jaguars Highlight Top Picks)

The San Francisco 49ers, New York Jets, Arizona Cardinals, and New York Giants were the only four teams that managed to pull off an upset in the opening week of the NFL season.

Mike Kadlick was our one writer last week who successfully backed an underdog, taking the Jets to upset the Titans in Tennessee.

We're back again for another week of upset picks with plenty of games to target in Week 2.

Mike Kadlick, NFL Senior News Writer
Gilberto Manzano, NFL Staff Writer
Mitch Goldich, Senior Editor
Iain MacMillan, Senior Editor, Betting
Peter Dewey, Associate Managing Editor, Betting

All odds listed are via DraftKings Sportsbook

Mike Kadlick Week 2 Upset Pick

Cincinnati Bengals (+124) vs. Houston Texans

The Bengals are coming off a Week 1 win over the Buccaneers that saw their offense put up 26 points, and their defense put up seven of their own—along with four turnovers. They head to Houston in Week 2 to take on a Texans team that had high expectations coming into the season and is on the verge of starting 0–2 for a second year in a row. That’s what I’m ultimately predicting will happen, with Cincinnati’s high-powered offense getting the better of Matt Burke’s defense.

Gilberto Manzano Week 2 Upset Pick

New York Giants (+280) vs. Los Angeles Rams

I think this is a bold pick, but I’m not sure anymore after how poorly the Rams played in the season opener against the 49ers. To make matters worse, L.A. will be without Myles Garrett for at least the next month. As for the Giants, they have a surplus of pass rushers, who looked extremely fast against the Cowboys last week. It could be a long night for the Rams’ offensive line, which struggled in Australia. It didn’t seem possible a few weeks ago, but there’s now a real chance the Rams open the season 0–2.

Mitch Goldich Week 2 Upset Pick

Jacksonville Jaguars (+124) vs. Denver Broncos

I’ll join the chorus taking the Jaguars to win in Denver, which includes more than half of the panel in our MMQB staff picks. (Maybe they should be favored?) I don’t want to overreact to Week 1, but the Broncos were pretty underwhelming on both sides of the ball against the Chiefs. Now they go back to their unique home-field advantage at high altitude, but do so on a short week after playing on Monday Night Football. They also do so against a really good Jaguars team that essentially had a tune-up game in a Week 1 route against the Browns. For one week, these looked like two teams headed in opposite directions, and I’ll bank on that trend continuing for at least another week.

Iain MacMillan Week 2 Upset Pick

Minnesota Vikings (+180) vs. Chicago Bears

The Chicago Bears' Week 1 win might be one of the biggest overreaction spots in recent history. I'm going to sound like a huge statistics nerd here, so I apologize in advance. I understand that 59 points is 59 points, but at the end of the week, the Bears finished 15th in Net Yards per Play (0.2), largely due to a terrible defensive performance. Chicago was 22nd in opponent EPA per play and 20th in opponent success rate. If you think defense doesn't matter, just look at the Cowboys last season, who had a top-three offense in football and missed the playoffs entirely.

Meanwhile, Brian Flores and the Vikings' defense have caused him some fits throughout his career. The Bears' offense is going to meet its match in this game, and Williams will be pressured by the Vikings' pass rush throughout. If they can wreak havoc, the Bears' defense is going to allow Minnesota to stay in the game.

This matchup is prime for an unexpected Week 2 upset.

Peter Dewey Week 2 Upset Pick

Jacksonville Jaguars (+124) vs. Denver Broncos

I know, I picked Denver to upset Kansas City in Week 1 and was proven very wrong, so I’m going in a different direction in Week 2.

The Broncos were the No. 1 team in defensive success rate and No. 7 in defensive EPA/Play last season, but they struggled with tackling in Week 1 against Kansas City, missing 28 tackles and allowing 247 yards after those misses.

The Broncos defense missed 28 tackles against the Chiefs, allowing 247 yards after missed tackles, the most yards allowed by any defense in a game since at least 2018.

The Broncos had eight different defenders miss multiple tackles on the night.#DENvsKC | #ChiefsKingdom
— Next Gen Stats (@NextGenStats) September 15, 2026

It was a shocking display, and I don’t think things will get easier against Trevor Lawrence and the Jaguars, who dominated Denver late in the 2025 season and put on an offensive clinic in Week 1 against the Cleveland Browns.

This is a step up in class for the Jags in theory, but the Broncos’ offense was lifeless in Week 1 with Davis Webb as the playcaller. Jaylen Waddle and Courtland Sutton combined for just three receptions for 13 yards, and Bo Nix turned the ball over multiple times.

Jacksonville was No. 8 in EPA/Play on defense in Week 1, and I trust Liam Coen’s offense a little more entering this game. The Broncos have held steady as 2.5-point favorites, but this line could come down closer to kickoff. After all, the Jags beat Denver by two touchdowns in Week 16 last season.

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