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Anthony Gould of the Oregon State Beavers reacts after scoring a touchdown against the Montana State Bobcats during the third quarter at Providence Park on September 17, 2022 in Portland, Oregon.
Anthony Gould of the Oregon State Beavers reacts after scoring a touchdown against the Montana State Bobcats during the third quarter at Providence Park on September 17, 2022 in Portland, Oregon. Photo by Amanda Loman/Getty Images via AFP.

James Madison is set to play its first conference game at the FBS level on Saturday. With a rest advantage and multi-point betting line move on their side, are the Dukes worth backing as +225 underdogs against the Sun Belt’s resident giant-killer, Appalachian State? Here are our top college football upset picks for Week 4.

For the most part, chalk held firm in college football this past week. That didn’t stop SBR’s weekly “Disaster Watch” column from handing out yet another outright winner. We very nearly had two upset results go our way at that. Unfortunately, Old Dominion fell to Virginia on a game-winning field goal as time expired.

Luckily, Tulane came through for us later in the day by winning over Kansas State as a two-touchdown underdog on the road. After cashing at 5-1 odds, it’s only fitting to have the Green Wave featured once again in this week’s column. Only this time, Tulane is the team that is getting put on upset alert!

Here are our top college football upset picks for Week 4 (odds via FanDuel Sportsbook and Caesars Sportsbook).

College Football Upset Picks for Week 4

Week 4 College Football Upset Predictions

James Madison (+225)

In many ways, James Madison is the modern-day version of what Appalachian State was a decade ago. Upon making the jump from the FCS ranks to the Sun Belt Conference, the Mountaineers have been very successful. This is only the Dukes’ first year at the FBS level, but similar success is likely on the horizon.

It’s fair to debate the significance of James Madison's big win against FCS-level Norfolk State, but JMU’s thrashing of Middle Tennessee two weeks ago is tougher to ignore. The same can be said for a spread that has come down two full points despite nearly 80% of all bets being on the Mountaineers.

Defensively, the Dukes have held opponents to 16.5 or fewer points in five straight seasons since reaching the FCS National Championship Game in 2017. Through the first two games of 2022, the Dukes’ defense has allowed a grand total of 21 yards rushing! 

To top it all off, James Madison has had two weeks to prepare for this high-stakes showdown. While App State was busy hosting ESPN’s College Gameday and beating Troy on a miracle Hail Mary last week, the Dukes were on a bye and gaining a rest advantage for their conference opener.

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Southern Mississippi (+400)

The Golden Eagles won only three games a year ago, due in part to a rash of injuries. The quarterback position in particular was a revolving door of chaos. After losing its top three QBs to season-ending injuries, Southern Miss wound up playing 10 different players at the position over the course of last season.

Through the first three games of 2022, second-year coach Will Hall has once again rotated several players in at quarterback. However, splitting reps between returning starter Ty Keyes and true freshman Zach Wilcke is completely different than having to play running backs Frank Gore Jr. and Antavious Willis at the position.

Tulane’s defense has been very impressive to begin the season. However, the Green Wave must avoid getting caught reading their press clippings following last week’s Power 5 win. Given all of the wrinkles and unpredictability of the Southern Miss offense and a ground game that is capable of sucking the air out of the football, the Golden Eagles figure to be highly competitive on Saturday.

Oregon State (+205)

Another team featured in SBR’s college football betting “Disaster Watch” column for the second straight week is USC. Any chance Fresno State had of springing a road upset over the Trojans went up in smoke when quarterback Jake Haener was carted off in the third quarter of last week’s game. USC rolled to the win and climbed to No. 7 in this week’s AP Poll.

USC has caught its fair share of breaks in the process of starting the season 3-0. After enjoying a plus-4 turnover margin in each of the first two games against Rice and Stanford, the Trojans benefitted from Haener’s injury last week. USC again had a plus-2 advantage on turnovers over the Bulldogs.

To say that the Trojans are primed for some regression in the takeaways department would be an understatement. Enter an Oregon State defense that has totaled eight takeaways through its first three games.

After playing in their first bowl game since 2013 last year, the Beavers have looked even better in getting out to a 3-0 start. Oregon State dominated Boise State in Week 1 before pulling out a last-second score to beat Fresno State on the road two weeks ago. Last Saturday, the Beavs dropped 68 points on a Montana State team that played in the FCS title game last year.

Where to Bet on College Football Upset Picks

Here are our top-rated sportsbooks:

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College football Week 4 upset picks picks made 9/21/2022 at 6:04 p.m. ET