College Football Straight Up Picks for Every Top 25 Game in Week 4 (Illinois Will Upset Indiana)

Iain MacMillan | Sep 16, 2025

Illinois is a road underdog against Indiana in a college football Week 4 showdown. / Ron Johnson-Imagn Images

It's time to start looking ahead to Week 4 of the 2025 college football season.

Many of the top teams are on BYE this week, including Georgia, Ohio State, Penn State, and Texas A&M. Even with that being the case, we have plenty of games involving Top 25-ranked teams that are available for us to bet on

In this article, I'm going to give you my straight-up pick for every game involving a Top 25-ranked team. We don't care about point spreads here; all we care about is who gets the win.

All odds listed in this article are via FanDuel Sportsbook

College Football Week 4 Picks for Every Top 25 Game

Texas Tech vs. Utah Prediction and Pick

Pick: Utah -152

In a battle between two of the top teams in the Big 12, it's the Utah Utes that stick out to me as the superior team. Their advanced metrics have been significantly better this season, including ranking seventh in the country in adjusted EPA per play at +0.43, well above Texas Tech, which comes in at 23rd at +0.21. That's enough for me to back Utah as a home favorite in this one.

UAB vs. Tennessee Prediction and Pick

Pick: Tennessee (Odds Not Available)

Oregon State vs. Oregon Prediction and Pick

Pick: Oregon (Odds Not Available)

Michigan vs. Nebraska Prediction and Pick

Pick: Nebraska +116

The advanced metrics between these two teams are extremely similar. They rank 15th and 17th in adjusted EPA per play, but it's Nebraska that has a slight edge in Net Yards per Play at +3.63, compared to Michigan at +2.57. With the Cornhuskers set as home underdogs, I'm going to take a shot on Nebraska in this Big Ten showdown.

Kent State vs. Florida State Prediction and Pick

Pick: Florida State (Odds Not Available)

Tulane vs. Ole Miss Prediction and Pick

Pick: Ole Miss -450

Auburn vs. Oklahoma Prediction and Pick

Pick: Oklahoma -220

Both Auburn and Oklahoma have gotten off to undefeated starts to their seasons, but I think Oklahoma is the only one between these two squads who are a legitimate contender to make the College Football Playoff. Oklahoma ranks eighth in the country in adjusted EPA per play, while Auburn ranks 19th. John Mateer is one of the best quarterbacks in college football and will lead the Sooners to a win in this game.

Purdue vs. Notre Dame Prediction and Pick

Pick: Notre Dame -4500

Temple vs. Georgia Tech Prediction and Pick

Pick: Georgia Tech -3000

South Carolina vs. Missouri Prediction and Pick

Pick: Missouri -520

Florida vs. Miami Prediction and Pick

Pick: Miami -295

Georgia State vs. Vanderbilt Prediction and Pick

Pick: Vanderbilt -4500

Illinois vs. Indiana Prediction and Pick

Pick: Illinois +158

Illinois is an interesting underdog pick if you want to bet on an upset this week. The Fighting Illini rank 13th in the country in adjusted EPA per play, while Indiana comes in at 20th. Neither team has had a tough schedule to start the year, but the Illinois 45-19 win against Duke was the most impressive of the bunch.

Sam Houston State vs. Texas Prediction and Pick

Pick: Texas (Odds Not Available)

Michigan State vs. USC Prediction and Pick

Pick: USC -820

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