College Football Straight Up Picks for Every Top 25 Game in Week 5 (Oregon vs. Penn State Prediction)

Iain MacMillan | Sep 24, 2025

Bet on Oregon to upset Penn State in Week 5 of the college football season. / Grace Smith/IndyStar / USA TODAY NETWORK via Imagn Images

We're truly in the thick of the 2025 college football season and fans are in for a treat this week with a loaded slate of games including plenty of marquee matchups.

In this article, I'm going to give my pick for which team will win every game involving a Top 25-ranked team. We don't care about point spreads here; moneyline winners is all we're aiming for. Let's dive into them.

All odds listed in this article are via FanDuel Sportsbook

College Football Week 5 Picks for Every Top 25 Game

No. 8 Florida State vs. Virginia Prediction and Pick

Pick: Florida State -255

No. 24 TCU vs. Arizona State Prediction and Pick

Pick: TCU +110

I've become a big TCU guy, and I believe in this team more than the betting market does. Josh Hoover has all of a sudden entered the Heisman Trophy conversation, and their offense has the ability to put up points in bunches against most teams in the country. Now, Hoover and the TCU offense will take on an Arizona State team that has allowed 6.6 yards per pass attempt his season. This looks like another good matchup for the Horned Frogs.

No. 16 Georgia Tech vs. Wake Forest Prediction and Pick

Pick: Georgia Tech -580

No. 22 Notre Dame vs. Arkansas Prediction and Pick

Pick: Arkansas +146

I'm out on Notre Dame. The Fighting Irish are 79th in the country in adjusted EPA and are now only continuing to get respect based on brand recognition. Meanwhile, Arkansas is 14th in adjusted EPA per play and have a net yards per play of +2.58 with a success rate of +10.3%. I'll back the Hogs as underdogs.

No. 21 USC vs. No. 23 Illinois Prediction and Pick

Pick: USC -240

USC is second in the country in adjusted EPA per play, and now the Trojans get to face an Illinois team that was exposed last week against Indiana. USC averages a whopping 9.1 yards per play this season, the best mark in the country, and now the Trojans will face an Illinois defense that ranks 102nd in opponent yards per play, allowing 6.1 yards per snap. The USC offense could have a field day in this one.

Utah State vs. No. 18 Vanderbilt Prediction and Pick

Pick: Vanderbilt -2100

No. 11 Indiana vs. Iowa Prediction and Pick

Pick: Indiana -295

Auburn vs. No. 9 Texas A&M Prediction and Pick

Pick: Texas A&M -230

No. 4 LSU vs. No. 13 Ole Miss Prediction and Pick

Pick: Ole Miss -114

No. 1 Ohio State vs. Washington Prediction and Pick

Pick: Ohio State -320

No. 15 Tennessee vs. Mississippi State Prediction and Pick

Pick: Tennessee -310

Arizona vs. No. 14 Iowa State Prediction and Pick

Pick: Arizona +190

No. 17 Alabama vs. No. 5 Georgia Prediction and Pick

Pick: Georgia -152

Are we ready to look past Alabama's Week 1 loss to Florida State? I'm certainly not. It'd be hard to convince me not to back Georgia in this spot.

No. 6 Oregon vs. No. 3 Penn State Prediction and Pick

Pick: Oregon +142

The advanced metrics in this game seem to point toward this marquee matchup being close enough that we should jump at the chance to back the Oregon Ducks as underdogs. The Ducks lead the country in adjusted EPA per play, while Penn State comes in at seventh in that stat. Oregon also has a net yards per play of +3.56, while Penn State sits at +1.90. That's enough for me to back the Ducks.

Massachusetts vs. No. 20 Missouri Prediction and Pick

Pick: Missouri (Odds Not Available)

No. 25 BYU vs. Colorado Prediction and Pick

Pick: BYU -240

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