TAMPA, Fla. (AP) -- Louisville's potent offense was no match for South Florida's tenacious defense.
Brohm was intercepted three times and his backup, Hunter Cantwell, was picked off once. The Cardinals also lost three fumbles while being held to 405 yards, well below their Big East-leading season average of 497.6 per game.
Louisville (5-6, 2-4) turned the ball over on the opening kickoff and never recovered.
Trent Guy fumbled returning the kick, USF's Nate Allen picked up the loose ball at the Cardinals 3 and continued into the end zone, a place the Bulls would visit five more times in the first half alone.
USF (8-3, 3-3) also scored on Trae Williams' 64-yard interception return and Ford's 6-yard TD that capped an 89-yard drive in which the freshman tailback also ran for 43 and 23 yards on consecutive plays.
Ford carried 24 times a week after posting the first 100-yard game of his career.
Brohm completed 18 of 37 passes for 213 yards while becoming the Big East's career passing leader. He tied the Cardinals' single-season record for TD passes with his 29th, but also was intercepted three times before being removed early in the fourth quarter.
At 5-6, Louisville's streak of nine consecutive bowl trips is in serious jeopardy. The Cardinals must win their finale against Rutgers to avoid a losing season and become bowl eligible, however that still may not ensure they'll get a berth.
A week after gaining a school-record 582 yards in a 41-10 rout of Syracuse that stopped a three-game losing streak, USF amassed 482 yards against a Louisville defense that has struggled all season.
Grothe was 17-of-23 for 194 yards, two touchdowns and one interception. He also rushed for 67 yards on 12 carries.
Brohm became the Big East's all-time passing leader on a 9-yard completion to Harry Douglas early in the second quarter. In three seasons since Louisville joined the league, he's thrown for 9,719 yards, boosting the senior's career total to 10,538.
Douglas scored Louisville's first touchdown on a 59-yard reception late in the second quarter. He finished with eight catches for 136 yards and also a 71-yard catch-and-run wiped out by a holding penalty.