Charlotte 49ers vs South Florida Bulls Prediction, Odds and Picks for Friday, 10/03/25

The Charlotte 49ers hit the road to take on the South Florida Bulls at Raymond James Stadium in Tampa in the second American Conference battle for the Niners. USF opens its league schedule with this Friday night game. Charlotte suffered a 28-17 loss at Jerry Richardson Stadium against Rice on Sept. 18, and it is 0-3 SU/ATS against FBS opponents this season, with just a win over FCS Monmouth (NJ) as its lone bright spot. And, even then, the 49ers barely won 42-35 in a shootout at home. The defense for Charlotte is rather shoddy, as it has allowed 28 or more points in three of four games. Its best effort was a 20-3 loss against Bill Belichick’s struggling North Carolina side on Sept. 6.

For South Florida, it was ranked for a hot minute after topping Boise State and Florida in the first two games, both as underdogs. However, USF was drilled 49-12 at Miami on Sept. 13, tumbling from the rankings. It rebounded last week with a 63-14 tune-up over FCS South Carolina State at home, but there are still plenty of questions. The defense has looked good outside of the Canes debacle, while the offense has been so-so. QB Byrum Brown is a solid dual-threat option, but he struggled against Florida and Miami a bit. He should find plenty of open spaces to do his thing about the 49ers, but the Bulls laying four touchdowns seems a bit much. Take Charlotte and the points, and hope its offense can give us something.

Charlotte +27 (-110) at time of publishing. Playable to +26.