Illinois vs. Indiana Prediction, Odds and Key Players to Watch for College Football Week 4

Ameer Tyree | Sep 18, 2025

Indiana wide receiver Elijah Sarratt (13) and quarterback Fernando Mendoza (15) are favored against Illinois. / Robert Goddin-Imagn Images

The Big Ten season kicks up a notch this weekend with several big games, and one of them will feature a pair of top-20 teams at Memorial Stadium on Saturday.

Illinois visits Indiana in a critical early matchup as both teams look to secure their first conference win of the season and improve to 4-0 overall. The Hoosiers are favored by less than a touchdown as hosts, but either team could come out on top.

Let's get into where we see the best betting edge ahead of the game. Here’s our full breakdown ahead of Week 4 starting with the odds from DraftKings Sportsbook.

Illinois vs. Indiana Odds, Spread and Total

Spread

• Illinois: +4 (-108)
• Indiana: -4 (-112)

Moneyline

• Illinois: +160
• Indiana: -192

Total

• 52.5 (Over -108/Under -112)

Illinois vs. Indiana How to Watch

• Date: Saturday, September 20
• Game Time: 8:00 PM EST
• Venue: Memorial Stadium
• How to Watch (TV): FOX
• Illinois Record: 3-0
• Indiana Record: 3-0

Illinois vs. Indiana Key Players to Watch

Illinois

Luke Altmyer: Altmyer is on a mission this season. The Illinois’ quarterback has thrown for 709 yards and eight touchdowns without an interception through three games. His rushing stats aren’t impressive, but he has scored a touchdown with his legs as well. Altmyer has connected with six different players on touchdown passes.

Indiana

Fernando Mendoza: Mendoza’s stats are eerily similar to Altmyer’s. He’s amassed 708 passing yards and nine passing touchdowns without an interception so far this season. Mendoza has notched a pair of rushing scores as well. He has a pair of star pass catchers out wide in Omar Cooper Jr. and Elijah Sarratt. Both of them help maximize Mendoza’s production. 

Illinois vs. Indiana Prediction and Pick

Illinois and Indiana have split their last five head-to-head matchups, but the Hoosiers have enjoyed more success against the spread. 

I mentioned that Indiana has more talent out wide, but there’s another disparity worth talking about in the backfields of these teams. 

The Hoosiers have an abundance of reliable running backs. Three have already eclipsed 200 rushing yards, while one more has crossed the century mark this season. All four of the aforementioned players are averaging at least 5.6 yards per carry. 

Indiana will be comfortable at home and can control the pace of this game to win straight up and cover. There’s more value in betting on the spread here, though. 

PICK: Indiana -4  (-112 at DraftKings Sportsbook)

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