On the eve of a loaded college football Saturday with six top-25 matchups, Friday, September 25, has five college football games on tap — including a tripleheader on ESPN.
The #5 Indiana Hoosiers will be the only top-25 team in action tonight, as they open Big Ten play vs. Northwestern at 8:00 p.m. ET. The American Athletic Conference (AAC) has two battles tonight, highlighted by Army. Clemson and California wrap up the night with a 10:30 p.m. ET kickoff for an ACC clash.
Below, we’ll highlight our best Friday college football picks for winners, spreads, and over/unders via PrizePicks.
Make your college football predictions on PrizePicks now!
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Friday College Football Picks for Winners, Spreads, Over/Unders
This week’s Friday college football picks feature Northwestern (2-0) vs. #5 Indiana (3-0) and Clemson (2-1) vs. California (2-1).
Following three non-conference games with an average margin of +43.0 points per game, Indiana opens Big Ten play vs. Northwestern, which cruised to a 41-7 win as 3.5-point favorites vs. Colorado last week.
Clemson and California opened the season with a loss; the Tigers fell 51-10 vs. #10 LSU, while the Golden Bears lost 45-24 vs. UCLA. Each team has bounced back with two consecutive wins, including 1 ACC dub.
Let’s take a closer look at each matchup, featuring winner payouts, spreads, and over/unders via PrizePicks.
PrizePicks data is live at the time of writing and is subject to change.
Northwestern vs. #5 Indiana Prediction on Spread – Friday, September 25
Time, How to Watch: 8:00 p.m. ET on FOX
Northwestern and Indiana have put up points in bunches thus far, with the Wildcats averaging 37.5 PPG and the Hoosiers recording 48.3 PPG.
After allowing 18 points and 432 total yards in a 34-18 win vs. an FCS opponent in South Dakota State, Northwestern bounced back by limiting Colorado to 7 points despite 348 total yards.
Indiana, the defending national champions, have looked as dominant as ever coming off back-to-back shutouts, featuring a 55-0 win vs. Howard and a 38-0 win vs. Western Kentucky. According to Game on Paper, IU’s +0.50 EPA per play ranks second nationally, but the Hoosiers’ strength of schedule (SOS) currently ranks 135th out of 138 FBS teams, per ESPN.
Northwestern’s SOS also ranks 117th, and it has fewer games under its belt with a 2-0 record. In summary, there’s still plenty of unknown entering this matchup due to each team’s quality of opponents thus far.
With that said, Indiana’s staff, led by head coach Curt Cignetti, and the Hoosier offense are likely the most dependable factors of this matchup.
This passing game has true NFL talent, as WRs Charlie Becker (13th) and Nick Marsh (32nd) are each within the top 32 prospects in the NFL Mock Draft Database’s 2027 NFL Draft consensus big board. Further, Indiana OT Carter Smith is ranked 35th on the board, anchoring strong pass protection that’s allowed a 10.8% havoc rate (81st percentile), via Fourth and Short.
TCU transfer QB Josh Hoover has looked the part as the fifth-best QB in 247 Sports’ transfer portal rankings. He’s totaled 216.7 passing yards per game and 12.7 yards per passing attempt through three games.
Most importantly, Hoover has only 1 turnover-worthy play over 51 passing attempts. That’s a 1.9% rate, a huge dip from last season’s 5.1% clip. PrizePicks gives Hoover 252.5 projected pass yards vs. Northwestern.
Game on Paper gives Indiana 0.76 EPA per passing attempt, sitting second out of 138 FBS squads. Furthermore, Fourth and Short’s explosiveness rating — measuring a team’s average predicted points added per successful passing attempt — places the Hoosiers third nationally.
Meanwhile, Northwestern gave up 285 pass yards vs. South Dakota State, followed by 180 rushing yards and 5.5 yards per carry against Colorado. The Wildcats’ success last week was anchored by forcing 4 turnovers, but Hoover has cleaned up his past turnover woes in the early going.
Northwestern’s 15.4% havoc rank is in the 42nd percentile, meaning it could struggle to pressure Hoover. Plus, Indiana is equipped with a run game that tallies 5.2 yards per carry (83rd percentile) and 0.15 EPA per rushing attempt (74th percentile).
Adding worry to the pass defense, the Wildcats’ standout nickel Braden Turnver, who has 13 tackles, 2 pressures, 1 PBU, and a pick-six, is out tonight.
Lock in your Northwestern vs. Indiana prediction on PrizePicks!
Clemson vs. California Prediction on Winner – Friday, September 25
Time, How to Watch: 10:30 p.m. ET on ESPN
Unlike Northwestern vs. Indiana, Clemson vs. California is trending toward a pick ‘em.
Following a 41-point loss at LSU, Clemson won only 22-7 as 19.5-point favorites vs. Georgia Southern. While the Tigers covered last week’s 28-20 win vs. North Carolina, they were up by only 1 point with 1:08 remaining on the clock. Instead of taking a knee, Clemson ran up the score.
There’s no facade behind California’s improved play. It won 21-18 on the road as 4.5-point underdogs vs. Syracuse, followed by a 49-7 win against Wagner a week ago.
Before we dig into the stats, the Golden Bears’ home advantage with a 10:30 p.m. ET kickoff should be circled. Clemson traveled about 2,500 miles from South Carolina to Berkeley, California.
Furthermore, the Tigers will be without CB Corian Gipson and DT Devarrick Woods on defense. However, this unit remains a strength with -0.24 adjusted EPA per play allowed (83rd percentile).
Clemson has been best against the pass by yielding -0.10 EPA per passing attempt (81st percentile). California heavily leans on its air attack with a 56.29% pass-play rate (83rd percentile), yet the unit lacks efficiency with 5.8 yards per passing attempt (18th percentile) and -0.14 EPA per passing attempt (22nd percentile).
Golden Bears QB Jaron-Keawe Sagapolutele, who has 259.5 projected pass yards tonight on PrizePicks, has 3 turnover-worthy plays over three contests. That’s a potential issue against a Clemson defense forcing 1.3 turnovers per contest (60th percentile).
On the flip side, Cal has stumbled against the run by conceding 5.8 yards per carry (seventh percentile) and 0.35 EPA per rushing attempt (fourth percentile).
The Tigers come off a successful day on the ground, totaling 186 rushing yards and 5.2 yards per carry vs. North Carolina. Clemson RB Gideon Davidson led the way with 16 carries for 105 rushing yards (6.6 YPC).
Davidson is projected for 77.5 rush yards vs. California, and he’s backed by an elite 4.95 yards after contact per attempt. The Golden Bears allow a 44.9% rush success rate (21st percentile) with a low 15.7% stuff rate (24th percentile).
Defense and a run game travel, and that’s where Clemson could have advantages on Friday night.
Predict the Clemson vs. California winner on PrizePicks.
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Make Friday College Football Picks on PrizePicks
Indiana opens Big Ten play with a favorable matchup through the air vs. Northwestern, while Clemson could make things ugly in Berkeley thanks to defense and a run game.
Don’t wait until kickoff — make college football picks on PrizePicks now. Just pick your players, predict More or Less on their stats, and cash in on your predictions if you’re right. With Team Picks, you can make predictions on game winners, spreads, and over/unders — now available in 36 states!
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