The 2025 college football season has already featured a number of surprises. USF dethroned two top-25 teams in the first two weeks of the season. Meanwhile, Dabo Swinney finds himself on the hot seat following Clemson’s poor 1-2 start. UCLA fired head coach Deshaun Foster following a disappointing 0-3 start while Virginia Tech ousted Brent Pry after an inexcusable loss versus Old Dominion. With Week 4 around the corner, we’ll break down some of the best upset picks of the week and detail which underdogs have the best chance of winning this weekend.
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Syracuse (+561) Over Clemson
Dabo Swinney promised to silence critics in his news conference ahead of Saturday’s matchup against Syracuse but there are a lot of reasons to like the Orange in this one. Syracuse comes in with the nation’s third-best passing offense and Clemson has really struggled to stop opponents through the air. Quarterback Steve Angelo leads the nation in passing but Syracuse is still looking for a marquee win to add to its resume.
On the other hand, the Tigers pass defense ranks 94th in the country after giving up 226.7 yards per game through the air. Clemson also has concerns along the offensive line, which has hurt Clemson’s run game through the first three weeks. If this game turns into a shootout, there’s a good chance that the Tigers could be on upset alert in Week 4.
Tulane (+320) Over Oklahoma State
The outlook for Tulane’s season changed when former BYU quarterback Jake Retzlaff transferred to the program late in the summer. The Green Wave suddenly find themselves as potential CFP hopefuls following a 3-0 start and for good reason. Led by Retzlaff, Tulane is averaging 222 rushing yards per game and will be up against Ole Miss’ 117th-ranked run defense. Retzlaff leads the team in rushing with 288 yards on the ground and has yet to throw an interception in 78 pass attempts. This game is going to be a shootout, so we’ll side with the better and more experienced quarterback in this one. At +320 odds, Tulane might be one of the best upset picks of the week.
South Carolina (+289) Over Missouri
South Carolina opened last week at 8.5-point favorites at home against Vanderbilt but everything changed when Heisman Trophy candidate LaNorris Sellers was knocked out of the game following a helmet-to-helmet hit in the second quarter. Sellers finished 6-of-7 passing for 94 yards and backup Luke Doty failed to lead a single scoring drive in his absence. Sellers is currently questionable but has been trending towards playing this week, though it wouldn’t be a surprise if he missed Saturday’s SEC clash as a precaution. If he does play, this line will move quickly and South Carolina could even be favored before kickoff.
