Indiana vs. Iowa Prediction, Odds and Key Players to Watch for College Football Week 5

Indiana is a road favorite as it looks to move to 5-0.

Indiana Hoosiers quarterback Fernando Mendoza is the favorite to win the Heisman this season. / Robert Goddin-Imagn Images

The Indiana Hoosiers are 4-0 and coming off a 53-point win over a top-10 team (at the time) in the Illinois Fighting Illini heading into their Week 5 matchup against the Iowa Hawkeyes. 

Indiana made the College Football Playoff in the 2024 season, and Curt Cignetti’s team looks poised to make it back in the 2025 season with one of the best offenses in college football.

Not only do the Hoosiers have the current Heisman favorite in Fernando Mendoza, but they rank third in the country in offensive EPA/Play.

As a result, they're favored by more than a touchdown in Week 5 against a 3-1 Hawkeyes team. Iowa lost to the Iowa State Cyclones in its second game of the 2025 season, but it has rebounded with double-digit wins over UMass and Rutgers in the last two weeks. 

Can Mark Gronowski and the Hawkeyes pull off a major upset?

Here’s a breakdown of the odds, a key player to watch and my prediction for this Big Ten clash. 

Indiana vs. Iowa Odds, Spread and Total

Odds via DraftKings Sportsbook

Spread

• Indiana -7.5 (-105)
• Iowa +7.5 (-115)

Moneyline

• Indiana: -298
• Iowa: +240

Total

• 48.5 (Over -110/Under -110)

Indiana vs. Iowa How to Watch

• Date: Saturday, Sept. 27
• Time: 3:30 p.m. EST
• Venue: Kinnick Stadium
• How to Watch (TV): Peacock
• Indiana record: 4-0
• Iowa record: 3-1

Indiana vs. Iowa Key Player to Watch

Fernando Mendoza, Quarterback, Indiana

While Mendoza isn’t a massive favorite to win the Heisman – he’s currently +800 in the latest odds – he’s gotten off to a fast start in the 2025 season.

The Hoosiers quarterback leads Division-I with 14 touchdown passes, and he’s completed 76.8 percent of his passes for 975 yards in the 2025 campaign without throwing a single interception. Mendoza has also chipped in two scores on the ground on 22 carries.

The Indiana offense is elite, ranking third in the country in EPA/Pass and 24th in EPA/Rush this season. Mendoza will look to keep things rolling against a tough Iowa team that is 42nd in EPA/Play on defense in 2025. 

Indiana vs. Iowa Prediction and Pick

The Iowa defense deserves some love in this game, as the Hawkeyes gave up just 16 points to Iowa State and have allowed less than 10 points in two games already this season.

However, facing Indiana is another level, and the Hawkeyes have struggled at times on offense this season, ranking 98th in the country in EPA/Pass.

The Hoosiers are No. 2 in the country in EPA/Play overall, and they’ve done it with an offense that is No. 3 in success rate overall and No. 2 in success rate throwing the ball. 

Defensively, they rank ninth in the country in EPA/Play, holding a ranked Illinois team to just 10 points in Week 4. Overall, Indiana has allowed just 33 points in four games, holding each opponent to 14 or fewer points. 

I am worried about an Iowa offense that relies a ton on the run (averaging over 200 yards per game on the ground) holding up against this Indiana squad. Not only can the Hoosiers score in bunches, but they rank 12th in the country in defensive success rate against the run.

After dominating Illinois in Week 4, I think Indiana is a little undervalued in this game – even on the road. 

Pick: Indiana -7.5 (-105 at DraftKings)

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Odds refresh periodically and are subject to change.

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