College Football Bets: Expert Picks Against Spread for Top-25 Week 4 Games

The college football schedule makers deserve a shout out, because the Week 4 slate is absolutely stacked.

There are six games scheduled between teams ranked in the AP Top 25. That’s the most in one weekend since December 2023, and that was when the conference championships were being held. This is simply a Saturday in September.

For many teams, conference play is continuing or starting up this week. And while the majority of the ranked teams are still undefeated, a handful have already suffered a loss. Another defeat before October would make for quite an uphill battle in the pursuit of a spot in the College Football Playoff.

Now, let’s go over that schedule. Starting us off in the early window is No. 1 Texas at No. 14 Tennessee. ESPN’s “College GameDay” is headed to Knoxville for the Longhorns’ first game against the Volunteers since they joined the SEC. (This is also the fourth week in a row the show is in SEC country and its second Texas game.)

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Staying in the SEC, No. 4 Ole Miss heads to the Swamp to take on No. 21 Florida. The Rebels are riding high after last week’s win over LSU and Lane Kiffin, though they might be without star running back Kewan Lacy (shoulder) against a Gators team off to its best start since 2019. Also in the afternoon slot in Big Ten country, No. 18 Michigan hosts No. 17 Iowa. The purpose of this column is to pick every game against the spread, but we must note that the total in this contest is just 38.5 points. (“If you don’t like that, you don’t like Big Ten football!”)

The primetime tripleheader is equally loaded, which makes for a quality quadbox. No. 23 Texas A&M plays at No. 10 LSU in a game between two teams that cannot afford a loss. The Aggies’ defeat to Kentucky was more damning than the Tigers’ loss at Ole Miss, but the loser of this game will miss the CFP in all likelihood. No. 20 Oregon is in a similar situation on the road against former Pac-12 rival No. 12 USC. The Ducks lost to Oklahoma State two weeks ago. It’s hard to know what to make of the Trojans, though. They have put up impressive offensive numbers but almost gave away the game against Rutgers last week.

And finally, No. 19 Missouri travels to take on No. 24 Mississippi State. You can practically hear the cowbells ringing now. The Bulldogs are ranked for the first time since 2022 thanks to the play of star quarterback Kamario Taylor. The Tigers have their work cut out for them on the road against a high-powered offense.

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Those are your six ranked games to watch on Saturday, but the fun hardly stops there. Defending national champion No. 5 Indiana has its Big Ten opener on Friday against Northwestern. No. 7 Ohio State also begins conference play at home against Illinois. And a spiraling Oklahoma squad will try to correct course on the road against No. 2 Georgia, which was literally practicing during breaks in its SEC opener against Arkansas last week. No pressure, Sooners.

There are still some non-conference games on the schedule projected to be blowouts (we’re looking at you, Miami!), but the action across the board projects to be much more competitive this weekend.

As you know by now, Athlon Sports picks every top-25 game against the spread each week. My colleagues Steven Lassan, Tyler Schuster and I are all still in the black after three weeks. Let’s keep it that way! Here are our picks:

College Football Picks Against the Spread for Week 4 Top-25 Games

Week 4 College Football Best Bets

Steven Lassan: No. 15 Utah vs. Iowa State — 7.5 Utah
Iowa State is a tough out in Ames, and despite a ton of new faces on the roster, first-year coach Jimmy Rogers has this team playing hard. However, I like Utah to cover the 7.5 points on Saturday. The Utes are strong again on defense, as coach Morgan Scalley’s group has allowed just 24 points through three games and only 3.8 yards per play. Iowa State’s offense thrived in matchups against SEMO and Bowling Green but was limited to 4.8 yards per play and just 255 yards against Iowa in Week 2. The Cyclones also rank last in the Big 12 in passing offense, which will be tough to keep pace against Utah’s one-two punch at quarterback Devon Dampier and Byrd Ficklin. Both defenses rank in the top 25 nationally in success rate, but there’s a significant edge on offense for the Utes right now.

Kyle Wood: Oklahoma vs. No. 2 Georgia — Georgia -14
The Sooners have scored three touchdowns in their last two games. The Bulldogs have scored 16. Sometimes, it really is that simple. Oklahoma’s offense is broken. Going on the road between the hedges — where Georgia has been almost unbeatable under coach Kirby Smart — is not the fix for whatever is ailing this group. For all the Sooners’ issues, their defense is still holding opponents under 10 points per game. But the Bulldogs can counter with the No. 1 scoring offense in the country. They’ll be able to move the ball at home.

Tyler Schuster: No. 4 Ole Miss vs. No. 21 Florida -3 — Ole Miss +3
Ole Miss is in an obvious let-down spot after an emotional game last week against former coach Lane Kiffin. But the Rebels have the most dangerous quarterback in college football and a defense that held up well in the passing game last week. I’m placing my trust in Trinidad Chambliss and Pete Golding to find a way to win a trick game on the road in The Swamp.

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This story was originally published by Athlon Sports on Sep 24, 2026, where it first appeared in the College Football section. Add Athlon Sports as a Preferred Source by clicking here.