College Football Straight Up Picks for Every Top 25 Game in Week 4 (Florida Will Beat Ole Miss in SEC Showdown)

We're three weeks into the college football season, but the meat of the 2026 campaign begins this week as most teams are past the cupcake portion of their schedule and are ready to begin conference play.

As I do each week, I'm going to give you my pick to win any and every game involving a team currently ranked in the top 25. We don't care about point spreads in this article, I'm just trying to pick winners.

College Football Week 4 Picks

Odds via Caesars Sportsbook

Northwestern vs. No. 5 Indiana Prediction

Pick: Indiana -2500

Wake Forest vs. No. 16 Louisville Prediction

Louisville has gotten off to a 2-1 start to its season, including a 41-31 win against SMU in its first ACC game of the year. Their offense has been electric, so there's no reason why they can't get the win against an inferior Wake Forest team.

Pick: Louisville -530

Sam Houston State vs. Texas Tech Prediction

Pick: Texas Tech N/A

No. 1 Texas vs. No. 14 Tennessee Prediction

In my betting preview for this game, I made the case for taking Tennessee the pull off the upset:

I'm selling my stock on the Longhorns. Manning has not lived up to expectations, and this offense has averaged just 5.3 yards per play, which ranks 78th in the nation. Last week against UTSA, he threw for just 164 yards on 4.9 yards per pass attempt. Thankfully, their run game has been good enough to lead them to a comfortable win, but they won't be able to do that against the Volunteers.

Meanwhile, Tennessee ranks 18th in the nation in yards per play, averaging 6.6 yards per snap. They have scored 42+ points in each of their first three games.

With the Volunteers at home, I'm going to take Tennessee as my upset pick of the week.

Pick: Tennessee +182

Illinois vs. No. 7 Ohio State Prediction

Pick: Ohio State -5000

No. 3 Notre Dame vs. Purdue Prediction

Pick: Notre Dame -5000

No. 15 Utah vs. Iowa State Prediction

Pick: Utah -345

Oklahoma vs. No. 2 Georgia Prediction

Pick: Georgia -590

No. 4 Ole Miss vs. No. 21 Florida Prediction

I think Ole Miss is a fraudulent team. There's no denying that Trinidad Chambliss is a Heisman candidate, but their defense hasn't been as good they have to be to hang with teams like Florida, who are averaging 7.7 yards per play this season. The Gators may be legitimate SEC contenders.

Pick: Florida -157

No. 17 Iowa vs. No. 18 Michigan Prediction

I don't care that Michigan beat Oklahoma in Week 2; I'm still not convinced the Wolverines are a good team, and Oklahoma's performance last week proved that their win against them may not be that impressive after all.

The Iowa defense is going to give the Michigan offense plenty of fits. The Hawkeyes may not need to score much to pull off this upset.

Pick: Iowa +180

No. 25 Houston vs. Georgia Southern Prediction

Pick: Houston -1000

Wisconsin vs. No. 13 Penn State Prediction

Pick: Penn State -380

Central Michigan vs. No. 6 Miami Prediction

Pick: Miami N/A

South Carolina vs. No. 8 Alabama Prediction

Pick: Alabama -500

No. 23 Texas A&M vs. No. 10 LSU

Pick: LSU -345

No. 20 Oregon vs. No. 12 USC Prediction

Pick: Oregon -165

No. 19 Missouri vs. No. 24 Mississippi State Prediction

Watch out for Mississippi State. The Bulldogs could be for real. They're averaging 7.7 yards per play this season, the third-most in all of college football. Their quarterback, Kamario Taylor, has also entered the early Heisman Trophy conversation.

They're going to further prove themselves with another strong win against Missouri in Week 4.

Pick: Mississippi State -230

Missouri State vs. No. 22 SMU Prediction

Pick: SMU N/A

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