Old Dominion vs. South Florida odds, line: 2025 college football picks for Cure Bowl matchup from proven model

The Old Dominion Monarchs face the USF Bulls in the 2025 Cure Bowl on Wednesday. Old Dominion closed the regular season with five consecutive wins, while South Florida won their last two games and three of four. The Monarchs (9-3), who finished second in the Sun Belt East Division at 6-2, outscored their opponents by 161 points this season. 

The Bulls (9-3), who finished tied for fourth in the American Conference, outscored their foes by 236 points in 2025. South Florida quarterback Byrum Brown and Old Dominion quarterback Colton Joseph have both opted out and will not take part in the game. South Florida coach Alex Golesh and most of the offensive staff will also not coach since they are at Auburn.

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Kickoff from Camping World Stadium in Orlando, Fla., is at 5 p.m. ET. This will be the first-ever meeting. The Bulls are 4-point favorites in the latest Old Dominion vs. South Florida odds, while the over/under for total points scored is 52.5 via SportsLine consensus. 

Before making any Old Dominion vs. USF picks, be sure to check out the college football predictions and betting advice from the SportsLine Projection Model.

The model simulates every FBS game 10,000 times, and it is profitable on its top-rated money-line picks since the beginning of the 2024 season. Anyone following could have seen impressive returns.

The model has simulated Old Dominion vs. South Florida 10,000 times and the results are in. We can tell you that the model is leaning Over, and it also says one side of the spread hits well over 50% of the time!

So who wins Old Dominion vs. South Florida, and which side of the spread hits well over 50% of the time? Join SportsLine right now to see which side of the spread you need to jump on, all from the computer model that has crushed its college football picks!

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