College Football Straight Up Picks for Every Top 25 Game in Week 6 (Oregon Will Continue to Roll)

Iain MacMillan | Sep 30, 2025

Oregon is favored against Indiana in Week 6 of the 2025 college football season. / Ben Lonergan/The Register-Guard / USA TODAY NETWORK via Imagn Images

We're five weeks into the college football season, and while we've learned a lot, there's still more to find out. Plenty of questions will be answered this week when a handful of teams that have gotten off to strong starts will face their toughest challenge to date, including when Indiana takes on Oregon in a Big Ten showdown.

In this article, I'm going to give my pick for which team will win every game involving a Top 25-ranked team. Point spreads don't matter in this article; all we care about is picking the winner. Let's dive into them.

All odds listed in this article are via FanDuel Sportsbook

College Football Week 6 Picks for Every Top 25 Game

West Virginia vs. No. 23 BYU Prediction and Pick

Pick: BYU -1000

Kentucky vs. No. 12 Georgia Prediction and Pick

Pick: Georgia -1700

No. 22 Illinois vs. Purdue Prediction and Pick

Pick: Illinois -375

No. 14 Iowa State vs. Cincinnati Prediction and Pick

Pick: Cincinnati -122

Wisconsin vs. No. 20 Michigan Prediction and Pick

Pick: Michigan -950

No. 24 Virginia vs. Louisville Prediction and Pick

Pick: Louisville -245

Boise State vs. No. 21 Notre Dame Prediction and Pick

Pick: Notre Dame -1250

No. 16 Vanderbilt vs. No. 10 Alabama Prediction and Pick

Pick: Vanderbilt +315

Can Vanderbilt pull off another upset against Alabama? Their advanced metrics have been fantastic this season, ranking fourth in adjusted EPA per play (+0.35) along with a Net Yards per Play ranking of +3.18. I still haven't forgiven Alabama for that terrible Week 1 performance against Florida State.

No. 9 Texas vs. Florida Prediction and Pick

Pick: Texas -275

Kent State vs. Oklahoma Prediction and Pick

Pick: Oklahoma (Odds Not Available)

No. 11 Texas Tech vs. Houston Prediction and Pick

Pick: Texas Tech -450

Minnesota vs. No. 1 Ohio State Prediction and Pick

Pick: Ohio State -3500

Mississippi State vs. No. 6 Texas A&M Prediction and Pick

Pick: Texas A&M -630

No. 3 Miami vs. No. 18 Florida State Prediction and Pick

Pick: Florida State +158

It's time to buy low on Florida State after the Seminoles' Week 5 loss to Virginia. They outrank Miami in adjusted EPA per play and Net Yards per Play. I think they bounce back with a win in this key ACC matchup.

No. 8 Indiana vs. No. 2 Oregon Prediction and Pick

Pick: Oregon -410

Oregon might just be the best team in the country, ranking second in the country in adjusted EPA at +0.41, and their win against Penn State last week showed that the Ducks are for real. I think they knock Indiana drop down a peg on Saturday.

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