DeAndre Hopkins made two catches for 75 yards on the game's opening drive, including a 45-yard touchdown pass from Kyle Parker, but the Tigers gained just 178 yards the rest of the way.
Fourteen drives, 178 yards.
For the first time in 40 years, Clemson (6-6, 4-4 ACC) has lost consecutive games to rival South Carolina (9-3, 5-3 SEC).
"A couple of their touchdowns came off of luck plays," said Hopkins, who finished with seven catches for 124 yards. "We gave them the ball and gave them opportunities to score."
South Carolina scored 29 unanswered points after the touchdown.
Spencer Lanning connected on the first of his three field goals (46, 25, 37) at the end of the Gamecocks' opening drive, which was kept alive by an un-sportsmanlike conduct penalty at the end of a third-down stop.
The Gamecocks then took a 9-7 lead on a 5-yard touchdown pass from Stephen Garcia to Patrick DiMarco. The drive was setup by a high snap that was bobbled by Dawson Zimmerman and downed at the nine yard line.
Antonio Allen also returned a third quarter interception 37 yards for touchdown to give the Gamecocks a 26-7 lead.
"We were kind of our own worst enemy, early in the game," said Clemson head coach Dabo Swinney. "We just were doing some things that weren't really smart. You can't do that against a good team. They'll take advantage of it, and they did that."
Parker, who completed just 7 of 17 passes for 117 yards, was benched after the interception.
Tajh Boyd played the rest of the way, going 10 of 18 for 73 yards.
"The pick-6 was just really costly," Swinney said. "That was just a really bad mistake. That really hurt us, as far as the momentum in the third quarter."
Alshon Jeffery inflicted his share of pain, too.
The sophomore from Calhoun County had five catches for 141 yards and a touchdown—a 47-yard strike from Garcia, who went 14 for 30 with 227 yards.
"He's the guy that makes a lot of plays," Swinney said of Jeffery. "He's a good football player. Outside of him, he was really the one guy that hurt us in the passing game."
After getting burned on the ground during last season's loss in Columbia, Clemson managed to keep the South Carolina running game quiet.
Freshman Marcus Lattimore was held to just 48 yards on 23 carries.
"They executed when they needed to and they got the job done," said Da'Quan Bowers. "You can't take anything away from those guys. I thought we had a decent game. We could have made a few more plays, but overall, I thought the defensive effort was great."
Offensively, things weren't so great.
"I think we had some chances to make some plays," said offensive coordinator Billy Napier, who will meet with Furman next week to discuss the vacant head coach job. "We didn't make them. We didn't rush the ball effectively. We weren't very good on third-down."
Swinney said players will be given time off this week before next week's bowl selection is announced.
Clemson is likely to end up in one of four bowls—Sun, Meineke Car Care, Music City or Independence. A representative from the Independence Bowl was scouting Saturday night's game.
Whichever one it is, Hopkins hops it will be the start of something good.
"We've got to start off with this bowl game. Hopefully, we'll have a streak. Alabama, not too long ago, before they won the national championship, their record kind of looked like ours," he said. "The next year they came out, they had a bunch of guys that played and know how it felt to lose. We've just got to recuperate."
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