NFL Upset Predictions and Picks for Week 3 (Will Texans Get First Win of Season vs. Jaguars?)

Iain MacMillan | Sep 18, 2025

The Texans are underdogs against the Jaguars in NFL Week 3. / Trevor Lawrence: Courtney Culbreath/Getty Images, C.J. Stroud: Tim Warner/Getty Images

We have seen no big upsets this NFL season. Favorites of four points or more are undefeated in 2025. We're likely to see that trend flip the opposite direction at some point, and when it does, we're going to see a plethora of upsets. Is this week the time for that to happen?

The SI Team is back to give their upset picks for Week 3 action. Let's dive into them.

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

Clare Brennan Week 3 Upset Pick

Patriots +105 vs. Steelers (via DraftKings)

New England struggled to get home last season, but the Patriots’ pass rush appears to be improving under Mike Vrabel. The Patriots currently lead the league in sacks with nine through the season’s first two games (perhaps take that number with a grain of salt, given their Week 2 opponent). While Vrabel’s defense still has a long way to go, the team could find similar success against the Steelers, disrupting Aaron Rodgers, who looked unsettled under pressure against the Seahawks. Pittsburgh has struggled offensively, especially on the ground, giving the Patriots’ defensive unit an opportunity to find its footing.

Mitch Goldich Week 3 Upset Pick

Texans +102 vs. Jaguars (via DraftKings)

This line feels like an overreaction to the Texans’ 0–2 record, but my opinion of Houston hasn’t changed much from what I thought coming into the season. This is a good-but-not-great team that had a chance to win in the final minutes (Week 1) and seconds (Week 2) against two clear NFC playoff teams in the Rams and Buccaneers. I think the Texans still have the talent to take care of business against inferior opponents, as they did last year when they went 5–1 against the rest of the AFC South.

I found the Jaguars’ loss last week really disappointing, to blow a game even after they picked off Jake Browning three times. I figured they would lose the minute Trevor Lawrence threw an interception in the end zone when they had a chance to go up 14–0 early, and they couldn’t capitalize. It’s a road game on a short week for Houston, but I think the better team will prevail.

Gilberto Manzano Week 3 Upset Pick

Cardinals +135 vs. 49ers (via Caesars)

I boldly predicted the Cardinals would win the NFC West this season, so it’s only right that I back them here for their first true test of the season. Arizona only defeated New Orleans and Carolina by one score in the first two games of the season, but the much-improved defense did enough to close out both games despite the stagnant offense. Even if Kyler Murray struggles again, this Cardinals’ defense has enough talent to force Mac Jones into killer mistakes.

Matt Verderame Week 3 Upset Picks

Cowboys +100 vs. Bears (via DraftKings)

The Bears not only look awful coming off a 52–21 thrashing to the Lions, but they’re also dealing with a host of injuries on their defense, including the losses of corners Jaylon Johnson and Kyler Gordon, and linebacker T.J. Edwards.

None of that bodes well for Chicago against the Cowboys, who come into Soldier Field having scored 40 points against the Giants. While Dallas isn’t a powerhouse, does it need to be with the Bears struggling so badly to play consistently on either side of the ball? Dak Prescott has been dealing through two weeks, throwing for 549 yards despite CeeDee Lamb’s repeated drops on big plays in Week 1. 

Caleb Williams and the offense have shown flashes of playing well, but they’ve failed to string together one good drive after the next. Considering how beaten up the Chicago defense is, that’s not going to be good enough facing the explosive Cowboys.

Iain MacMillan Week 3 Upset Pick

Texans +102 vs. Jaguars (via DraftKings)

The Texans’ offense has some issues that they need to work out, but given that Nick Caley is just two games into being the team’s offensive coordinator, I’m willing to look past some early-season hiccups. What I’m most intrigued by is the Texans' defense, which has done a great job shutting down great offenses in both the Rams and Buccaneers. Now, the Texans' defense gets to take on a Jaguars offense that has had issues of their own with Trevor Lawrence’s consistency and Brian Thomas Jr.’s unwillingness to take a hit.

The Texans are a great underdog bet to get their first win of the season.

Peter Dewey Week 3 Upset Pick

Cardinals +135 vs. 49ers (via Caesars)

Mac Jones did enough – and actually looked pretty good – for the San Francisco 49ers to beat the New Orleans Saints in Week 2, but I’m not buying it against a much tougher opponent in Arizona in Week 3.

The Cardinals haven’t won convincingly despite playing the Saints and Carolina Panthers, but the team has a dynamic offense that should be able to score enough to put the pressure on Jones to produce. Arizona also dominated the first half of its Week 2 game against Carolina before Bryce Young started to figure things out.

I just can’t buy Jones as a favorite in this matchup given his resume. 

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