College Football Bets: Expert Picks Against Spread for Top-25 Week 5 Games

It’s hard to believe the college football regular season is already a quarter of the way complete. We now have a solid sample size from which to form opinions on players, units and teams as conference play begins in earnest. But don’t let that lull you into complacency.

Just when you think you have a grip on the landscape of this ever-changing sport, in it chimes “Not so fast, my friend!” a la Lee Corso, leaving you wondering how such a heavy favorite could lose.

The Week 5 schedule is shockingly light compared to last week. There are only three games between top-25 teams, while five ranked squads are idle. ESPN’s “College GameDay” is finally leaving its month-long residency in SEC country in favor of the Big Ten. No. 5 Ohio State’s trip to play No. 14 Iowa gets the spotlight this week. The Buckeyes, the highest-ranked team with a loss, looked unstoppable last week. But the Hawkeyes looked inevitable in their last-second win against Ohio State rival Michigan.

If you’re wondering what else to watch this week, allow me to direct you to the aforementioned SEC country. No. 25 Missouri hosts No. 8 Florida, which is fresh off a huge win over Ole Miss in the Swamp. The Gators are gunning for their first ranked road win since 2018 against a Tigers team that lost a shootout last week at Mississippi State.

Speaking of the No. 16 Bulldogs, Kamario Taylor and Co. have a huge test on Saturday against No. 7 Alabama and ascendant quarterback Keelon Russell. The Crimson Tide are favored in Starkville, where they haven’t lost since 2007. Can Taylor (pardon the pun) turn the tide of this lopsided series?

• Related: Alabama’s Keelon Russell and Mississippi State’s Kamario Taylor are Efficiency Monsters

Outside of that top-25 trio of games, No. 24 Kentucky’s trip to South Carolina is huge for both programs. The Wildcats can further legitimize their strong start with another SEC road win. On the other side of that matchup, Gamecocks coach Shane Beamer is coaching for his job.

Back in the Big Ten, Washington heads south to face No. 18 USC. Pressure is also ramping up on coach Lincoln Riley after the Trojans’ loss to the Ducks. But the Huskies have also been a bit of a disappointment as the preseason top-25 squad lost to Minnesota at home last week. Over in the ACC, fans are pining for something resembling a test for No. 4 Miami, which has mowed through its schedule — and will likely continue to do so. Perhaps little ol’ Clemson can make life tough on the Hurricanes, who had a closer-than-expected call on the road against Wake Forest two weeks ago.

This weekend’s schedule is almost exclusively conference games. The two exceptions are No. 3 Notre Dame’s trip to North Carolina and FCS McNeese heading to No. 11 LSU. That said, the spreads are tighter across the board — the Cowboys-Tigers game is the only one with a spread north of 30 points this week.

Athlon Sports has picks for every top-25 against the spread every single week. My coworkers Steven Lassan, Tyler Schuster and I are clinging to our positive records through four weeks. We have every intention of keeping that up. Here are the picks:

College Football Picks Against the Spread for Week 5 Top-25 Games

Week 5 College Football Best Bets

Steven Lassan: No. 17 Tennessee vs. Auburn — Tennessee -7
Familiarity is a big storyline in this one, as former Tennessee assistant Alex Golesh brings Auburn to Rocky Top in hopes of a road upset over his former boss Josh Heupel. After giving up 44 points to Florida in Week 3, the Tigers got back on track defensively against Vanderbilt. However, Auburn’s secondary could be vulnerable against the Volunteers, as quarterback Faizon Brandon aims to rebound after struggling versus Texas last Saturday. Also, while the Tigers have talent in the trenches, it’s not quite up to the level the Longhorns brought to Knoxville last week, which should allow Heupel’s team to get back to its ground game. Tennessee’s ability to get pressure on the quarterback (19 sacks so far) is problematic for an Auburn offensive line that’s still searching for the right answers and has struggled to open up holes in the ground game.

Kyle Wood: Vanderbilt vs. No. 2 Georgia — Georgia -24.5
I’m going back to the well with the Bulldogs, who are on a short list of teams that have covered every game against the spread this season. The Commodores’ 3-1 record is a bit fluky (see: NC State), and their run game has taken a big step back. Going on the road against Georgia’s fearsome defense will not fix those struggles on the ground. And if Vanderbilt can’t establish it, then the Bulldogs’ pass-rushers will be able to tee off on freshman quarterback Jared Curtis (a one-time UGA commit). Coach Clark Lea has turned the ‘Dores into a respectable program, but it’s hard to look past the fact that Kirby Smart’s Bulldogs have outscored his teams 154-20 in three meetings since he arrived in 2021.

Tyler Schuster: No. 8 Florida -5.5 vs. No. 25 Missouri — Florida -5.5
A week after running roughshod over the Ole Miss defense, I don’t see a scenario where the Gators’ offense slows down. Jadan Baugh and Duke Clark have emerged as arguably the best one-two running back tandem in college football, and appear primed for another big outing. Last week, Missouri gave up 139 yards to Mississippi State. That spells trouble for the Tigers’ defense. I like the Gators, despite this game being a tricky spot after a huge win last weekend.

Related: Ranking All 138 College Football Teams After Week 4

Related: 2026 Bowl Projections After Week 4: Florida Joins Playoff Field, Oregon Rising

Related: College Football Rankings: Athlon Sports Top 25 (After Week 4)

This story was originally published by Athlon Sports on Oct 1, 2026, where it first appeared in the College Football section. Add Athlon Sports as a Preferred Source by clicking here.