NFL Week 4 upset alert: Why these five favorites could easily lose, including the 49ers

The dogs were BARKING in Week 3! In a slate where 12 games were decided by a single possession (tying an NFL record), the underdogs were able to have themselves a day. Eight underdogs won outright in Week 3, including four that we presented to you last week. 

We accurately pinpointed the Falcons, Browns, Colts and Broncos as teams that could pull off the upset, with our lone miss coming with the Titans. That said, Tennessee nearly helped us record a clean sweep as the Titans took the ball to the Giants' 7-yard line with a chance to score a game-winning touchdown with less than 30 seconds left in regulation. Alas, the upset hopes were quickly dashed, with Cam Ward throwing a game-clinching interception in the end zone. 

After sharpening our eagle eye for upsets last week, our attention turns to Week 4. Specifically, we're highlighting four road teams with a chance to pull off victories, along with a home dog that is very familiar with being in this position. 

NFL odds via FanDuel Sportsbook.

New York Jets (+3.5) at Chicago Bears

• When: 1 p.m. ET | Where: Soldier Field (Chicago)
• TV: Fox | Stream: (Fubo, try for free)
• Jets ML odds: +148

These aren't your father's Jets. No, they aren't going to win the Super Bowl or anything like that, but they're going to be a pesky thorn in the side of every team they play this season, which is more than you could say in the past. The biggest difference from last year to now is the stabilized play under center. Geno Smith leads the NFL with a 76% completion rate and is averaging 261.0 passing yards per game, while throwing four touchdowns and recording zero interceptions. So long as Smith keeps a clean sheet when it comes to turnovers, the Jets have enough talent to hang around long enough to possibly pull off the upset. 

Sure, the offense takes a hit with Breece Hall being sidelined with a thigh injury, but I think Braelon Allen will fill his shoes just fine, and the Jets back could exploit a big weakness of the Bears. The 6-foot-1, 235-pound back will face a Chicago run defense that is allowing 5.1 yards per carry, which is tied for second-most in the NFL. 

As for the Chicago side of things, Case Keenum's performance on Monday night was something out of a movie. But is it sustainable? Will he even get the nod, or will it be top backup Tyson Bagent now that he's cleared concussion protocol? Regardless, they'll have a sneaky tough matchup against a Jets defense that is allowing the second-fewest total yards per game (258.3) and tied for the fourth-fewest yards per play (4.8). 

Dallas Cowboys (+2.5) at Houston Texans

• When: 1 p.m. ET | Where: Reliant Stadium (Houston)
• TV: Fox | Stream: (Fubo, try for free)
• Cowboys ML odds: +120

I have a feeling Dallas will be champing at the bit to get back on the field to remove the sour taste of their Week 3 loss to the Ravens in Rio. Yes, the Cowboys' defense continues to be atrocious, allowing the third-most yards per game (387.0) and ranking in the bottom 10 in points allowed per game (27.3). 

That said, my question is this: Will that matter against the Texans? Houston is 0-3 on the season, and its offense continues to look lost. The Texans' 4.8 yards-per-play average and their 3.6 yards-per-carry rate are tied for the fourth-lowest in the NFL. They're also in the bottom half of the league on third down, converting on just 36.4% of opportunities. 

This is a bad vs. bad matchup between the Cowboys' defense and the Texans' offense, but I think I'm going to give the ever so slight edge to Dallas, especially if Houston wideout Nico Collins (hamstring) is out or limited after missing time. 

Meanwhile, the Cowboys' offense continues to be among the most prolific in the NFL, notching a league-high 61.5% drive scoring rate. Houston's defense hasn't been as lethal as it was a season ago, so if Dallas can jump out in front, it'll be a tall task for C.J. Stroud to claw the Texans back behind a questionable offensive line. 

There's also the home-field advantage question. Given that this game is in Texas, I wonder how many Cowboys fans will be in attendance at Reliant Stadium. Could it be closer to a 50-50 fan split? 

Denver Broncos (+2.5) at San Francisco 49ers

• When: 4:25 p.m. ET | Where: Levi's Stadium (Santa Clara)
• TV: CBS | Stream: Paramount+
• Broncos ML odds: +130

We're going back to the well with Denver as an upset candidate in Week 4, but this speaks more to the state of the San Francisco 49ers. As always seems to be the case, they're dealing with injuries. Notably for this matchup, wideout Mike Evans (ribs), left tackle Trent Williams (shoulder stinger), and linebacker Dre Greenlaw (quad) all got dinged up in last week's win over Arizona. Now, their statuses for Week 4 are in question. Even if they play, they may not be 100%, giving an edge to Denver. 

Specifically, Williams being out/limited for this matchup could loom large. The 49ers have yet to allow a sack this season, but that could change as they square off against a Broncos pass rush that is the top 10 in pressure rate and sacks through three weeks. 

While the Broncos' offense has been clunky through the first three weeks, the Niners did just allow Jacoby Brissett and the Cardinals' offense to drop 30 points, albeit in a win. The Broncos have also been pretty solid as an underdog, owning a 5-1 straight-up record in their last six games in that spot. 

Detroit Lions at Carolina Panthers (+3.5)

• When: 8:20 p.m. ET | Where: Bank of America Stadium (Charlotte, N.C.)
• TV: NBC | Stream: (Fubo, try for free)
• Panthers ML odds: +168

The Panthers are perennially overlooked, and folks have profited off of that over the last couple of years. Since the start of last season, Carolina is 6-3 ATS as a home underdog and 5-4 straight up. 

While the Lions look like a behemoth in this head-to-head because of their high-powered offense, it's their lackluster defense that puts them on upset alert. Pretty much across the board, the Detroit defense is either at or near the bottom of the league. 

Lions defense in 2026	Stats	NFL Rank
PPG allowed	31.7	Last
Total YPG allowed	416.7	31st
Passing YPG allowed	299.3	Last
Third-down percentage	56.1%	31st
Red zone TD percentage	84.6%	31st

Last week, Bryce Young and the Panthers' offense came back down to earth a bit, totaling just 18 points in a loss to Cleveland on the road. However, because they are facing this Lions defense, I think they'll look more like the offense that was averaging 35.5 points per game and 409.0 total yards per game over the first two weeks of the regular season. 

This has all the makings of a shootout, which may come down to the final possession. Do you know who was tied for second with six game-winning drives last season? Bryce Young. 

Atlanta Falcons (+2.5) at New Orleans Saints

• When: Monday, 8:15 p.m. ET | Where: Caesars Superdome (New Orleans)
• TV: ESPN, ABC | Stream: (Fubo, try for free)
• Falcons ML odds: +126

The Falcons looked like an entirely different team with Michael Penix Jr. at quarterback. They pulled off a dominating win over the Packers last Thursday night, which gives them the rest advantage over a Saints team that is reeling from a fourth second-half collapse against the Raiders. 

To make matters worse for New Orleans, Travis Etienne is sidelined with a hamstring injury, which dramatically limited their ground attack. Kendre Miller is averaging just 3.4 yards per rush, while Alvin Kamara is averaging 2.8 yards per rush. If New Orleans can't run the ball, that puts a lot of pressure on Tyler Shough, who turned the ball over on each of his final four drives on Sunday. 

The biggest X factor in this game, however, is Bijan Robinson. The Falcons' superstar back has an advantageous matchup against a Saints run defense that is allowing 4.7 yards per carry, tied for the fifth-highest in the NFL. After rushing for 194 yards last week, it wouldn't be surprising at all to see Robinson put another primetime game in a chokehold. 

Speaking of primetime, Atlanta has also been virtually unbeatable in this spot recently, owning a 5-0 record under the primetime spotlight since 2025. Conversely, the Saints are 0-5 in their last five primetime games.