Northwestern vs. #5 Indiana Prediction, Spread, NCAAF Picks – Friday, September 25

Five college football games take place on Friday, September 25, and the lone matchup featuring a ranked team pits Northwestern against #5 Indiana at 8 p.m. ET on FOX. Ahead of kickoff, the Hoosiers are 20.5-point home favorites in this Big Ten showdown.

Northwestern cruised to a 41-7 victory over Colorado in Week 3, giving the program a 2-0 record to begin the season. Indiana, the reigning champs, steamrolled Western Kentucky en route to a 38-0 win in Week 3 to improve to 3-0.

Below, we'll break down our Northwestern vs. #5 Indiana prediction and picks for Friday’s college football game, including the spread, over/under, and key player picks on PrizePicks.

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Northwestern vs. #5 Indiana Prediction, Spread, Over/Under – Friday, September 25

With Northwestern getting QB Aidan Chiles in the transfer portal from Michigan State, the Wildcats’ offense is ranked in the 90th percentile in passing success rate (56.3%) and 87th percentile in pass EPA/play (0.4), per Game on Paper.

It remains to be seen if Chiles and Northwestern’s aerial attack can have success against Indiana’s defense, which is in the 67th percentile in passing success rate (41.0%) and 79th percentile in pass EPA/play (-0.1) allowed.

This is the first time the Wildcats have begun a season with a 2-0 record since 2020, when the program went 7-2. After going 4-5 against Big Ten opponents last year, Northwestern is hoping to get its conference schedule started on the right foot in 2026.

Following the departure of QB Fernando Mendoza to the NFL, TCU transfer QB Josh Hoover has made it a seamless transition to Indiana. Among 132 college QBs with 50+ dropbacks in 2026, he has the second-most yards per attempt (12.7), fourth-most passing TDs (10), and 0 INTs across his first three starts.

The fact that the Hoosiers are in the 96th percentile in offensive EPA/play (0.4) and 89th percentile in defensive EPA/play (-0.1) despite only 55% of their 2025 roster returning is a testament to how quickly head coach Curt Cignetti has turned this program into a powerhouse.

Indiana currently returns the sixth-lowest payout to win the National Championship (7.14x) and second-lowest payout to win the Big Ten (3.44x) on PrizePicks.

Northwestern vs. Indiana Spread, Over/Under – Friday, September 25

Indiana enters Friday’s game as a 20.5-point home favorite against Northwestern, returning a 1.04x payout on PrizePicks if it wins outright.

Here are the full payouts for the Northwestern vs. #5 Indiana game on PrizePicks.

Make your Northwestern vs. Indiana pick on the spread or over/under on PrizePicks.

Payouts show potential returns on correct PrizePicks predictions. A 2x payout returns $200 on a $100 entry. Lower multipliers reflect outcomes users are picking as more likely. Payouts are live as of writing and subject to change.

Northwestern vs. Indiana Prediction on Over/Under – 9/25/26

Here are the key game stats and trends behind our Northwestern vs. Indiana prediction on the over/under for Friday, September 25’s game. 

• Both of these teams are capable of generating explosive plays through the air, with Northwestern residing in the 93rd percentile in yards per dropback (10.1). Meanwhile, Indiana is in the 99th percentile in yards per dropback (12.0).
• Dating back to last season, the Wildcats have scored 34 or more points in four of their last five games.
• The Hoosiers have notched 38+ points in five of their last six contests, including at least 52 points in two of their first three games in 2026.
• Northwestern is a perfect 2-0 to the over, and there were 65 points scored in the Big Ten Championship between these teams in 2024.
• Since Cignetti became the head coach at Indiana in 2023, the team has a conference-best 65.5% hit rate to the over against Big Ten foes, per Team Rankings.

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Northwestern vs. Indiana Picks, Player Stats for PrizePicks: 9/25/26

Here are the top Northwestern vs. Indiana picks to target on Friday, September 25. Today’s college football picks for PrizePicks include QB Charlie Becker, WR Turbo Richard, and RB Caleb Komolafe.

Indiana WR Charlie Becker vs. Northwestern: 30.5 Longest Rec

• Becker has recorded at least a reception of 35 or more yards in each of Indiana’s first three games this year.
• Of the 188 college WRs with 15+ targets, Becker has the seventh-most yards per reception (22.7) and fifth-most yards per route run (5.0), via Pro Football Focus.
• Additionally, Becker has hauled in all three of his contested catches, so it’s clear Hoover trusts him to come down with 50/50 balls.

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Indiana RB Turbo Richard vs. Northwestern: 16 Rush Attempts

• Although Richard has an elite name, he’s yet to carry the ball more than 15 times in a game this campaign.
• Richard splits the backfield workload with RB Lee Beebe Jr., who leads the Hoosiers in rushing attempts (47) to begin 2026.
• Beebe scored 2 goal-line TDs against Western Kentucky in Week 3, so he could be the preferred short-yardage back over Richard.

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Northwestern RB Caleb Komolafe vs. Indiana: 11.5 Rec Yards

• Komolafe has accrued 27+ receiving yards in both of his starts in 2026.
• Northwestern is a double-digit underdog, which could lead to a game script with more passing opportunities than usual.
• In the Wildcats’ offense, Komolafe has the third-most yards per route run (3.4) and a healthy 12.8 yards per reception on 5 catches.

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Make Northwestern vs. Indiana Picks on PrizePicks

Northwestern and Indiana will begin their Big Ten schedule on Friday. Even with the Wildcats and Hoosiers possessing solid defenses, both offenses boast enough weapons to light up the scoreboard.

Don’t wait until kickoff — make your Northwestern vs. Indiana picks on PrizePicks now and earn real money if you’re right.

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