USF (8-4, 4-3 Big East) scored on a fumble return and held Steve Slaton, the nation's No. 2 rusher, to his worst game as a starter.
Slaton saw his streak of six straight 100-yard games snapped. He ran for a season-low 43 yards, 115 below his average. The Mountaineers (9-2, 4-2) lost at home for the first time in nine games.
Grothe, the redshirt freshman, finished 21-of-29 for 270 yards and helped keep the nation's second-best scoring offense off the field.
West Virginia was effective only through the air. Pat White threw two touchdown passes to Brandon Myles but the Mountaineers squandered several other scoring chances. They had scored touchdowns on 77 percent of their drives inside the 20 entering the game, yet failed to reach the end zone four times inside the red zone against USF, including its first three drives.
The Mountaineers didn't score their first touchdown until midway through the third quarter. The nation's second-best rushing attack was limited to 132 yards.
Slaton fumbled the ball away at the USF 1 on the first drive of the second half. West Virginia got the ball back at the USF 28 after a punt and White found a leaping Myles with a 15-yard TD pass in the left corner of the end zone. But White's conversion pass fell incomplete to make it 14-12.
Grothe took the Bulls 70 yards on the next series, finding Ean Randolph with a 21-yard TD pass late in the third. He later converted a pair of third-down passes to keep alive a 14-play drive that resulted in a short field goal by Delbert Alvarado midway through the fourth and a 24-12 lead.
White found Myles with a 44-yard scoring pass with 5:16 left to cut the deficit to 24-19.
USF failed to get a first down on its next drive and West Virginia got the ball back at its 15. But a pass went off Myles' hands and Trae Williams intercepted the tipped ball for South Florida with 1:54 left. White finished 14-of-22 for 178 yards and ran for just 17 yards on 15 carries.
Eric Wicks intercepted a tipped pass on USF's fifth play from scrimmage, returning it 32 yards to the South Florida 11. But holder Travis McClintic was tackled at the 3 on a fake field goal and West Virginia was held scoreless in the first quarter for just the second time all season.
White was hit by Chris Robinson on a pass attempt and fumbled deep in West Virginia territory. USF's George Selvie scooped up the ball at the 9 and scored the Bulls' first defensive touchdown of the season for a 7-6 lead midway through the second quarter.
Grothe capped a 66-yard drive with a 10-yard keeper for a touchdown just before halftime to put the Bulls ahead 14-6. It marked the first time in 17 games that West Virginia was held without a first-half touchdown.
USF Upsets No. 7 West Virginia; 24-19
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