College Football Week 2 Early Picks & Predictions (2025)

Week 1 of the 2025 college football season is officially in the books. There were plenty of upsets, including Ohio State, the defending National Champions, knocking off No. 1 Texas in a 14-7 slugfest.

My Week 1 Early Picks & Predictions settled a perfect 3-0. Ohio State and Texas went under 47.5 with ease in a matchup between two of the nation’s top-three defenses in 2024. LSU and head coach Brian Kelly mounted a solid comeback effort against Clemson in the second half to win as an underdog in Death Valley, ending the program’s Week 1 woes. Carson Beck led the Miami Hurricanes to an impressive 27-24 win against Notre Dame, securing the win with a go-ahead field goal as home underdogs.

Let’s continue to monitor early line movement and place a few picks based on my latest predictions for Week 2. Follow me on X @Matt_MacKay to get updated college football betting analysis and insights, including more free picks, during each week of the 2025 college football season.

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College Football Week 2 Picks & Early Line Movement

(Odds courtesy of DraftKings Sportsbook)

Iowa vs. Iowa State (22)

After a thrilling win overseas in Week 0 against Kansas State, the Cyclones routed South Dakota 55-7 during their home opener in Week 1. Iowa State will host the Iowa Hawkeyes with an in-state rivalry game during Week 2.

The Hawkeyes beat Albany, a non-major program, 34-7 during their home opener. It’s going to be a step-up in competition against Rocco Becht and the Cyclones, who beat Iowa on the road with a walk-off field goal in 2024.

Iowa is starting Mark Gronowski at quarterback and features RB Terrell Washington Jr. and RB Xavier Williams in its backfield to replace last year’s workhorse, Kaleb Johnson. It’s clear that the Hawkeyes want to continue to be a team that sets the tone at the line of scrimmage.

Iowa State has a more prolific passing attack. The point spread moved from -2.5 to -3.0 on Iowa State as a road favorite. Meanwhile, the point total dropped from 43.5 to 41.5. The Hawkeyes couldn’t score 35 points against a non-major opponent and Gronowski only attempted 15 passes.

Kansas State’s running game was shut down in the second half by Iowa State’s defense. I expect a similar low-scoring affair in Ames, so let’s bet under 41.5 total points. This number has gone under in four of the last five head-to-head matchups between the Hawkeyes and Cyclones.

Pick: Under 41.5 (-112)

Michigan (14) vs. Oklahoma (18)

The marquee game in Week 2 sends the University of Michigan on the road in Norman against the Oklahoma Sooners. It’s a top-20 matchup that will show us a lot about both teams, who are coming off of double-digit wins against non-power 4 opponents in Week 1.

Bryce Underwood had a solid debut as Michigan’s QB1. The freshman, who was the No. 1 prospect in the 2025 recruiting class, finished Week 1 with a 67.7 percent completion rate for 251 yards and a touchdown. He committed zero turnovers, while RB Justice Haynes logged 9.9 YPC, 159 rushing yards and three touchdowns for the Wolverines.

Oklahoma QB John Mateer lit up Illinois State with a blistering 81 percent completion rate for 392 yards and three touchdowns. The Sooners’ offense struggled with Jackson Arnold for most of its games in 2024, so we’ll see how Mateer’s production translates against Michigan DC Wink Martindale’s defense on Saturday night.

The line has moved -3.5 in favor of Oklahoma at home. Mateer’s impressive passing display is likely the driving factor, along with Michigan’s defense allowing New Mexico to finish with 17 points and over 250 yards of total offense.

It’s tempting to bet another point total under in this game, especially with two defenses that finished top-30 in the country for points allowed per game last season. However, I’m going to grab the value that’s been driven onto Michigan at +6 on the point spread.

Underwood’s big arm and Haynes’ ability to produce out of the backfield will keep Oklahoma’s defense off balance. Mateer is going to be slinging the football, which could lead to a couple of turnovers for Michigan to leverage.

Instead of +2.5, we now have the Wolverines sitting at +6. Mateer has more experience but Michigan’s offense is revamped and their defense remains a stout unit. Let’s back Underwood in his first collegiate road game against a top-20 opponent in prime-time.

Pick: Michigan +6 (-110)

Arizona State (11) vs. Mississippi State

The Arizona Sun Devils looked solid during their Week 1 win over Northern Arizona. QB Sam Leavitt rushed for a pair of lengthy touchdowns, while WR Jordyn Tyson led all Sun Devils wideouts with 12 receptions for 141 yards and two touchdowns.

Mississippi State has QB Blake Shapen under center following an injury that derailed his 2024 campaign. The Bulldogs are attempting to put their 2024 2-10 record in the rearview mirror, with head coach Jeff Lebby returning for his second year in Starkville.

This is a huge game for Mississippi State in Week 2. Shapen and the Bulldogs pulled away from Southern Miss in the second half of their 34-17 Week 1 win. The program’s new QB1 looked good, finishing with a 76 percent completion rate for 270 yards and a touchdown. Running backs Davon Booth and Fluff Bothwell split carries, combining for three rushing touchdowns.

Neither team played a formidable opponent in Week 1. The Bulldogs hold home field advantage ahead of this prime-time interconference tilt. The Sun Devils went from -10 to -7 road favorites, indicating money is starting to flow into Mississippi State.

Arizona State won this matchup 30-23 at home last season. Now, they are without former RB Cam Skattebo, while facing a revamped Bulldogs offense led by a healthy Shapen.

I’ll back the home team as a touchdown underdog at +7 on the point spread. Shapen should be productive enough to keep the score to a one-possession game by the final whistle, especially playing a prime-time game at home.

Pick: Mississippi State +7.0 (-110)