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There are only three matchups featuring ranked opponents on both sides in Week 4 of the 2025 college football season with No. 17 Texas Tech battling No. 16 Utah, No. 9 Illinois visiting No. 19 Indiana and No. 11 Oklahoma facing No. 22 Auburn but that only means more chaos is in store. It's often these so-called "lull" weeks which produce the biggest upsets in the sport. Are the Red Raiders, Utes, Illini or Hoosiers among the best spread bets in Week 4? If you're interested in college football betting at top sportsbooks, here's five teams to back this week.

Best spread picks for Week 4

Syracuse +17.5 vs. Clemson

Can it get any worse for Dabo Swinney's Tigers? Clemson losing in Week 1 to LSU could've been chalked up as acceptable, but the fans had reason to worry after the team needed to mount a comeback to beat Troy after falling in a 16-point hole. The Tigers then lost to Georgia Tech at home to fall to 1-2 and now have a serious challenge to get back to the College Football Playoff. Syracuse got routed by Tennessee and needed overtime to beat UConn but the Orange got things right against Colgate. This team has historically given Clemson fits and I think 17.5 points is too much for a program that's in a tough spot.

SMU +7 vs. TCU

The Iron Skillet is on the line when these two Dallas-Fort Worth area programs line up against each other in Week 4. The Mustangs were on the wrong end of a shootout against Baylor and did not look convincing against Missouri State, but they're still bringing back a good contingent of a squad that made the CFP a year ago. The Horned Frogs have a star quarterback in Josh Hoover and have looked excellent in their two games, so there's a reason they're favored. I'd probably move this line up to +7.5 to avoid a push but I'll back the Mustangs here.

Maryland +10 vs. Wisconsin

The Terrapins have another opportunity for a statement game. In most most cases, they've folded. However, a lot of those contests have come against Michigan, Penn State and Ohio State. Wisconsin is not in the same class, despite what fans in Madison would have you to believe. The Badgers are coming off a humbling defeat at the hands of Alabama and have not looked great through three weeks. Meanwhile, Maryland is 3-0 and enters Week 4 after routing Towson 44-17. I'll back the Terps as road underdogs against a middling Wisconsin side.

Memphis +7.5 vs. Arkansas

Don't look now, but Ryan Silverfield has quietly put together an excellent football program in Memphis. The Tigers are looking for their third straight season with double-digit wins and head to Fayetteville with CFP aspirations. The Razorbacks haven't quite taken off yet under Sam Pittman, and they're coming off a tough loss to Ole Miss. Brendon Lewis is the better quarterback and that's good enough for Memphis to cover as a home underdog -- if not with outright.

No. 9 Illinois +5.5 vs. No. 19 Indiana

Many predicted Illinois would be in 2025 what Indiana was a year ago. So far, Bret Bielema's squad has held up its end of the bargain and looks like a CFP contender with Luke Altmyer at quarterback. He's thrown for 709 yards and eight touchdowns across three blowout wins but these are the games which can define a program. The Hoosiers want to show last year wasn't a fluke and they've got a star quarterback of their own in Fernando Mendoza. Could this be his Heisman moment? Even though the Hoosiers are at home, I think Illinois is the better team.