Driskel's rushing performance -- a school record for a quarterback -- included a 71-yard scoring run late in the game. The signal-caller also threw for 77 yards on 11-of-20 efficiency for the Gators (6-0, 5-0 SEC).
Mike Gillislee gained 67 yards on 17 rushes as Florida beat Vanderbilt for the 22nd straight time.
The Commodores (2-4, 1-3) lost despite getting 237 passing yards and a score from Jordan Rodgers.
Vanderbilt's Jordan Matthews made eight grabs for 131 yards and a touchdown.