The Pirates (5-1, 2-0) overcame a 10-point halftime deficit to remain unbeaten in American Athletic Conference play and are off to their best start since 1999.
USF (2-4, 1-1) faded in the second half against a ranked team for the second straight game. The Bulls were tied 3-3 at the half before losing 27-10 at Wisconsin.
Carden completed 13 of 15 passes for 134 yards while leading scoring drives of 84, 86 and 79 yards on East Carolina's first three possessions of the second half.
Marquez Grayson's 24-yard TD run trimmed USF's lead to 17-14 late in the third quarter and Breon Allen's 4-yard scoring run put ECU ahead 21-17 early in the fourth. Carden threw a 35-yard TD pass to Allen in the first quarter and Anthony Scott's 20-yard run left USF trailing by 11 with six minutes left.
Mike White threw for 257 and one touchdown for USF. Andre Davis, back after missing four games because of a bruised sternum, scored on a 51-yard reception and finished with six catches for 124 yards for the Bulls.
Marlon Mack scored on a 13-yard run for USF, however East Carolina limited the AAC's leading rusher to 61 yards on 15 attempts.
East Carolina entered the game ranked fourth in the nation in passing (395.6 yards) and total offense (581.4) and ninth in scoring (43.6) but fell well short of the numbers the Pirates are accustomed to accumulating. Carden was 24 of 33 for 250 yards and one interception.
The senior became the Pirates' career passing leader during last week's 45-24 conference opener against SMU and entered Saturday night on a streak of three consecutive 400-yard performances.
But with Mack, Darius Tice and Kennard Swanson all having some success running the ball, USF was able to keep Carden and the rest of East Carolina's playmakers off the field for extended stretches early. Once Carden established a rhythm, though, there was no slowing down the explosive Pirates.
Davis, meanwhile, brought some much-needed vitality to USF's passing attack. The senior was injured on his only catch of the season before Saturday night — a 44-yarder in the season opener against Western Carolina — and his first reception against East Carolina gave the Bulls a 7-0 lead.
White found the 6-foot-1, 207-pound receiver open on the sideline for a 25-yard gain that made Davis USF's career leader for receiving yards. He needs nine more receptions to become the Bulls' career leader in that category.
Justin Hardy had 10 receptions for 114 yards, moving him within 37 catches of the NCAA Division I-A career mark of 349 held by Oklahoma's Ryan Broyles. Allen finished with 124 yards rushing on 18 carries.