Old Dominion vs. USF prediction, odds: 2025 Cure Bowl matchup picks by proven model

The Old Dominion Monarchs face the South Florida Bulls in the 2025 Cure Bowl on Wednesday. Old Dominion closed the regular season with five consecutive wins, while USF won its 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 Golesh took the Auburn job.

Kickoff from Camping World Stadium in Orlando, Fla., is at 5 p.m. ET. This will be the first-ever meeting. The Bulls are 2.5-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. South Florida picks, check out the college football predictions from the SportsLine Projection Model. 

New users can target the DraftKings promo code, which offers $200 in bonus bets if your $5+ bet wins:

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. Anybody following those college football betting picks at sportsbooks and on betting sites could have seen strong returns.

Now, the model has set its sights on Old Dominion vs. South Florida. You can visit SportsLine now to see the picks. Here are the FBS college football odds and trends for USF vs. Old Dominion:

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How to make Old Dominion vs. South Florida picks

After 10,000 simulations of this matchup SportsLine's model is going Over (52.5) on the total. The Bulls have gone over the total in three of their last five games and in seven of 10. 

The model has Old Dominion running back Trequan Jones rushing for more than 80 yards and a score, while South Florida running backs Nykahi Davenport, Sam Franklin and Alvon Isaac combined to rush for more than 100 yards. The teams combine for 56 points as the Over clears in well over 50% of simulations.

The model also says one side of the spread hits well over 50% of the time. You can see the model's pick at SportsLine.  

So who wins Old Dominion vs. South Florida, and which side of the spread hits well over 50% of the time? Visit SportsLine now to see which side of the Old Dominion vs. South Florida spread to jump on, all from the advanced model that's up on its top-ranked money-line picks, and find out.