Indiana vs. Oregon prediction: Odds, picks, best bet for Saturday’s Big Ten headliner

The University of Indiana may just be a football school, after all.

After shocking the sport with a run to the College Football Playoff last winter, the masses believed that 2025 would be a step back for the Hoosiers. They’d still be good, but expecting a repeat performance was unfair.

Whoops.

Not only is Indiana undefeated, but the Hoosiers are ranked No. 7 and have the opportunity to jump even further up the board with an upset in Oregon on Saturday.

The bookies don’t see it happening — Indiana is a 7.5-point underdog — but doubt this team at your own risk.

Indiana vs. Oregon odds, prediction

There were a lot of skeptics (including the writer of this piece) who thought that Indiana’s hot start to 2025 was a bit of smoke and mirrors.

The Hoosiers didn’t play Old Dominion off the field in Week 1, and then they went flat-track bully for the next two weeks with blowout wins over Kennesaw State and Indiana State.

Oregon is once again a national title contender. Getty Images

Sentiment began to change the following weekend when Indiana obliterated Illinois, 63-10. It was a throttling, and it put quarterback Fernando Mendoza on everybody’s radar, whether for the Heisman or concerning the No. 1 overall pick in the 2026 NFL Draft.

The win over Illinois was eye-opening, but it was Indiana’s victory at Iowa that really got me on board. You’re not going to have an easy time playing at Kinnick Stadium, but the Hoosiers showed they can get in the mud. They’re not just a one-trick pony with Mendoza.

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Oregon is also elite on both sides of the ball, and the Ducks will have home-field advantage against a team traveling across the country.

But with both teams coming off the bye, the schedule spot isn’t that daunting.

And the numbers suggest that these two teams are really not that far apart.

Oregon is ranked No. 1 in the country per SP+, Bill Connelly’s catch-all metric, but Indiana is No. 3, boasting top-10 units on both sides of the ball.

Furthermore, Indiana’s offense, which blends efficiency and explosiveness, is built to hang in games like this. The back door should be open.

A trip to Autzen Stadium turns out to be a humbling experience for most teams, but Indiana isn’t most teams.

The Play: Indiana +7.5 (-118, FanDuel)

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Michael Leboff is a long-suffering Islanders fan, but a long-profiting sports bettor with 10 years of experience in the gambling industry. He loves using game theory to help punters win bracket pools, find long shots, and learn how to beat the market in mainstream and niche sports.