LOUISVILLE, Ky. -- Louisville made a case that it's as likely as any team to win the Big East.
The Cardinals knocked off No. 16 South Florida with a strong run defense, and a career day from a receiver who had been injured for most of the season. They also got some help from the Bulls, who committed 14 penalties for 109 yards.
The Bulls (6-2, 1-2) had a chance to get the ball back for one last drive with 1:19 left in the fourth quarter, but a defensive holding on a missed field goal by Louisville allowed the Cardinals to play keepaway.
South Florida's Matt Grothe threw for 344 yards and two touchdowns, but he also was picked off twice. His fourth-quarter interception gave the Cardinals (5-2, 1-1) the ball at USF 27 and allowed Louisville to run out the clock.
Cantwell threw for 212 yards and ran in Louisville's other touchdown from the 1. Long's two touchdown catches and 134 yards receiving were career highs. He missed the Cardinals' first four games with a broken foot.
How good was it for Cantwell to have him back?
"Very nice," the quarterback said. "Everyone has been telling how good he was, that he was a game breaker, and he showed it today."
Long's game was also memorable for a slip up that could have cost the Cardinals. An accurate pass from Cantwell bounced off Long's shoulder pads and was picked off by linebacker Kion Wilson, leading to Kelly's touchdown.
"Hunter came over to me and said, 'you're still the guy,' and that meant a lot to me," Long said.
Cantwell kept his word, throwing him the winning touchdown in the fourth quarter.
With Pittsburgh losing to Rutgers on Saturday and UConn knocking off Cincinnati, the Big East race is muddled behind first-place West Virginia. The Cardinals are in the thick of the chase, having bounced back well following a disappointing first season under coach Steve Kragthorpe.
"No doubt, it's a big win to get us back on track," defensive lineman Earl Heyman said.
The Bulls had been averaging 195 rushing yards per game, but the Cardinals held them to 8. Linebacker Jon Dempsey, the Cardinals' leading tackler for the season, had nine tackles and a sack. Heyman and Adrian Grady sacked Grothe twice each.
"We just didn't protect enough," USF coach Jim Leavitt said.
With Heyman dragging him down by his jersey, Grothe threw his second interception of the day, giving the Cardinals the final possession with 3:03 to play.
"He was just trying so hard to make something happen," Leavitt said. "I know you can't throw the interception, but that poor guy was just ... he didn't want to take a sack."
The Cardinals contained Grothe's running but when Louisville's pass rushers didn't pressure him, he had an easy time making completions. He was 30-for-40.
The Bulls struck first with a 32-yard field goal by Maikon Bonani in the second quarter but the Cardinals hit back with Cantwell's first touchdown to Long, a 69-yarder that was a career long for both players, and Long's first career touchdown catch.
Cantwell ran the ball in for Louisville's second touchdown of the quarter with less than a minute to go before halftime.
The Bulls drove 63 yards in 48 seconds but had to settle for another Bonani field goal from 24 yards with 2 seconds left in the half that made it 14-6.
Grothe threw a 3-yard touchdown pass to Kelly late in the third quarter to make it 14-13 and his 15-yarder to Busbee with 9:22 left in the fourth quarter gave USF a 20-17 lead.
The home team has won five straight games in the series.