College football picks and predictions for all 58 games in Week 5, straight-up and ATS

The college football schedule for Week 5 lightens up a bit, at least in terms of the number of games. It's the first week since Week 0 that we've had fewer than 70 games on the slate — and we actually have fewer than 60 on the slate. But don't for a second think that means the quality of game will suffer. Not only do we have three ranked-on-ranked matchups with Alabama vs. Mississippi State, Ohio State vs. Iowa and Florida vs. Missouri, but a number of ranked teams like Notre Dame, BYU, Miami and several others go on the road for tricky tests.

We've continued to roll with our college football picks and predictions this season, and we're not stopping. These are our picks for every Week 5 game with predictions both straight-up and against the spread across all 58 games.

2026 College Football picks record — Straight-Up: 270-50 (Last Week: 56-15) | Against-the-Spread: 169-150 (Last Week: 40-31)

College football picks for every Week 5 game, straight-up and ATS

Expert picks and analysis for the biggest Week 5 CFB games

Alabama (-5.5) vs. Mississippi State

Everyone in the world seems to be talking about Kamario Taylor and Mississippi State on the heels of their big win over Missouri. And rightfully so. Jeff Lebby's Bulldogs have made a distinct leap this season behind their sophomore quarterback and look the part of a legitimate Top 25 team in college football. Now, they get to really prove their moxie against a Top 10 team in the country as the Alabama Crimson Tide make the 90-mile drive to Starkville.

Unfortunately for those who bring cowbells with them on Saturdays, this might be just a slight mismatch. While Taylor and the Mississippi State offense in terms of their caliber should be able to match what Keelon Russell and Co. are able to offer, the fact of the matter is that Alabama has a defense that's capable of winning a national championship. The Bulldogs simply can't say the same and, while Mississippi State will undoubtedly throw some haymakers of their own, it won't be enough to cover in this matchup.

Notre Dame (-21.5) vs. North Carolina

Because it's always easy to not fully trust Notre Dame and because North Carolina has at least looked notably better than they were a year ago, it feels like people are making this some sort of big game this week. The unfortunate reality of the situation, however, is that the Fighting Irish might simply be able to smush the Tar Heels in this matchup.

It will be interesting to see how UNC's defense is able to handle the Notre Dame offense. For much of the year, the Notre Dame rushing attack has been middling at best, which is something to watch against a higher level of competition. Furthermore, the Tar Heels defensive front is a legitimate strength that could pressure CJ Carr and make things difficult at times. That might be the only thing that goes right for them in this matchup, however.

The North Carolina offense is quite putrid and matches up against one of the best defenses in the sport. The likeliest game script here is that UNC's defense is able to keep it close for about a half but ends up being on the field too much, which then allows Notre Dame to pull away and cover.

Ohio State (-13.5) vs. Iowa

The Iowa Hawkeyes and Ohio State Buckeyes have played twice in the 2020s. While both game were played in Columbus and not in Kinnick, the results of those games have been a 54-10 win for Ohio State in 2022 and a 35-7 win in 2024. These are obviously different teams, but that also might even be more of a reason to take the Buckeyes in this matchup.

We're probably seeing the Hawkeyes get a bit too much respect for upsetting a pretty average Michigan team last week. But let's not forget that Bryce Underwood produced two 100-yard receivers in that game as well. Iowa's defense is not as strong, especially in the secondary, as it's been in past years, and now has to try and stop Jeremiah Smith. And while Iowa's offense is fine, it certainly doesn't have the look of a group that can truly withstand Ohio State's front for 60 minutes.

Strange things happen in Kinnick. It just doesn't seem like Ohio State is the right team to expect that against this week.

Florida vs. Missouri (+5.5)

Everyone just watched Florida put a hurting on Ole Miss in The Swamp last week, and now the Gators are the toast of the town in college football. Deservedly so, it should be said. Buster Faulkner's offense with Aaron Philo and Jadan Baugh is electric, and they should undoubtedly be able to put up some points on a good-not-great Missouri defense. But this is also a Florida defense that hasn't exactly been nails and another road test for the Gators who, if you remember, were trading blows with Auburn on the road prior to the win over the Rebels.

I firmly maintain that Florida is the better team in this matchup. They have bigger aspirations and a higher ceiling that Mizzou. Moreover, history has taught us that, even with a number still next to the Tigers' name, they aren't to be fully trusted in this type of game. Yet, with the environment in Columbia this weekend, Florida could have just enough discombobulation while Mizzou's offense is capable of putting up a number that the Tigers keep this close — but I'm still taking Florida to stave off the upset straight-up.

BYU vs. TCU (+6.5)

Another ranked team going on the road and, quite frankly, I'm worried about this spot for BYU. That's not to say that I think TCU is better than BYU, because that's far from the case in this matchup. Yet, as they make their way to Fort Worth, the Cougars might play into the Horned Frogs' hand simply with their style of play. TCU quarterback Jaden Craig struggles mightily when pressured but has flashed when he's given time. Well, BYU ranks just 71st in pass rush grade this season and has been middling in coverage as well.

Perhaps more notably, TCU has a Top 12 defense against the run this season according to PFF grades and is the only run defense the Cougars have faced this season that ranks inside the Top 100 of those grading metrics. That's not the end-all, be-all here, but it could force Bear Bachmeier and this offense into some passing situations where they'll need to prove themselves. To me, that's a game that could be quite tight until very late, and I'll give TCU the edge while playing at home.

Miami (-16.5) vs. Clemson

Everyone has been trying to talk themselves into Clemson showing improvement and being able to hang with Miami, or at least give the Hurricanes a scare, in this game. That could not possibly be me. Tait Reynolds and Clemson have been the 10th-worst offense this season according to PFF and now has to contend with the Miami defensive front. Even with the injuries for Mario Cristobal's team coming into this matchup, this feels like a complete mismatch.

In reality, the "turnaround" for Clemson since getting dog-walked by LSU probably has way more to do with playing Georgia Southern, UNC and Cal than it does with the Tigers actually being meaningfully better and showing up better against legitimately elite competition. Their defense won't have enough answers to even give their offense a chance against Miami — and I'm not sure their offense has a chance anyway.

Note: All odds are courtesy of FanDuel Sportsbook. Odds change periodically and are subject to change. If you or someone you know has a gambling problem and wants help, call 1-800-GAMBLER.

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