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Indiana Hoosiers vs. Iowa Hawkeyes prediction, pick for CFB Week 5 on Saturday 9/27/25

Indiana Hoosiers vs. Iowa Hawkeyes prediction, pick for CFB Week 5 on Saturday 9/27/25

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By: Bryan Armetta

In a season already filled with major upsets, last Saturday provided an all-time shocker. Indiana defeating Illinois wasn’t too surprising — this was a playoff team in 2024, after all. It was the final score, a 63-10 drubbing, that caught everyone, fans and pundits alike, off guard.

Now, the 11th-ranked Hoosiers will hope to keep the momentum going against another Big Ten opponent. However, another offensive outburst might prove difficult against a stingy Iowa defense. Which of these two conference rivals will come out on top this afternoon? Below is my prediction and pick for College Football Week 5’s game between the Indiana Hoosiers and the Iowa Hawkeyes.

Indiana enters this contest as 8.5-point favorites (-105) over Iowa, with the over/under set at 48.5 points on DraftKings Sportsbook.

Indiana vs. Iowa prediction, preview

Clearly, Indiana was able to do whatever it wanted vs. Illinois. The team compiled a whopping 579 total yards of offense, led by quarterback Fernando Mendoza. The junior threw for 267 yards and five touchdowns while completing 21 of his 23 passes (91.3%). Right now, the Cal transfer leads all of FBS with 14 passing touchdowns. Could this be the start of a dark horse Heisman campaign? It’s not out of the question.

On the ground, Mendoza is joined by the running back quartet of Kaelon Black, Roman Hemby, Khobie Martin and Lee Beebe. All four Hoosiers have compiled at least 200 rushing yards. Right now, Indiana ranks fourth in college football with 312.4 rushing yards per game. Three games against non-Power 4 programs have certainly helped. Regardless, those numbers are nothing to sneeze at.

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Saturday’s game is a true battle of polar opposites. Iowa has allowed just 66.7 rushing yards per game, tenth-lowest in the nation. Through four games, the Hawkeyes have held their opponents to a combined 58 points (14.5 PPG). However, it was the offense that came through last Friday during a 38-28 win over Rutgers. Quarterback Mark Gronowski has been solid so far, gaining 492 passing yards and three touchdowns. On the ground, the junior has tallied six rushing touchdowns. It isn’t Indiana-good, but Iowa also wields four different running backs with at least 90 rushing yards.

Indiana vs. Iowa pick, best bet

The Hawkeyes, while improved on offense, will need to put up a stellar effort on defense. Giving up 28 points to the Scarlet Knights isn’t the most positive sign heading into this contest. That’s not to say Rutgers is bad, but Indiana is in a different tier. It helps Iowa that Saturday’s matchup will be held at Kinnick Stadium.

It’s worth noting that there isn’t much to judge Indiana by. As previously mentioned, the school’s first three wins came against lackluster competition. I expect IU to rank among the best offensive units in college football this season. Still, that doesn’t mean this group won’t run into a speed bump or two along the way. After such an exhilarating win, this week has all the makings of a trap game. Although the Hoosiers are too talented to fade entirely, I’ll back the Hawkeyes to cover at home.

Best Bet: Iowa +8.5 (-115)

Bryan Armetta is a New York-based writer that has spent over eight years in sports media. Working for DraftKings since 2024, he currently serves as a writer, editor and analyst for all things sports and pop culture. Bryan specializes in MLB, NBA, NFL, college sports and entertainment content. Prior to his time at DKN, he worked for MLB Network, NHL Network and SiriusXM Sports.
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