The Gamecocks (4-0, 2-0 Southeastern Conference) won on defense, holding the Commodores (3-1, 1-1) to 77 yards.
South Carolina is 4-0 for the first time in coach Steve Spurrier's seven years with the team.
But it was frustrating for the coach. Quarterback Stephen Garcia threw four interceptions.
Garcia did throw his third touchdown pass, as many as defensive end Melvin Ingram has now scored this season. Ingram recovered a teammate's fumble in the end zone to go with two sacks, a tackle for an 8-yard loss and swatted away a pass.
Garcia's problems caused Spurrier to throw his headset in the first quarter and his playcalling sheet in the second. By the time Garcia threw his fourth pick in the end zone in the fourth quarter, the Head Ball Coach could do nothing more than slowly shake his head as Garcia spoke to him.
Spurrier put backup Connor Shaw into the game in the fourth quarter, his first action since getting the nod to start this year's opener, then being benched after an ineffective first quarter. Spurrier took no chances, running Lattimore on six of Shaw's first eight plays. The other two snaps were designed quarterback runs.
Lattimored finished 77 yards rushing and 73 receiving.
Ace Sanders led South Carolina with four catches for 75 yards. All-SEC receiver Alshon Jeffery had just two receptions for 34 yards.
Garcia did throw a 52-yard touchdown pass to Lattimore in the waning moments of the second quarter that put South Carolina ahead 14-3. But the sophomore running back did most of the work, dodging tackles and picking up a nice block from receiver Nick Jones for the score. Lattimore also scored on a 22-yard run in the third quarter.
South Carolina's defense had struggled for the first three games, allowing 372 yards a contest. But they harassed Vanderbilt quarterback Larry Smith all night, finally knocking him out of the game in the third quarter.
Smith was 12-of-16 passing, but they were almost all short throws. He threw for 44 yards and was sacked six times. Backup Jordan Rodgers, whose older brother is Green Bay Packers star Aaron Rodgers, completed his first two passes, but only gained 2 yards.
Zac Stacy was Vanderbilt's leading rusher with 18 yards on seven carries, while Jonathan Krause caught nine passes for 55 yards.
South Carolina freshman defensive end Jadeveon Clowney forced two fumbles. One of them came after he leaped over a blocker and grabbed Smith's arms, forcing the ball from the Vanderbilt quarterback's hands in the third quarter.
Casey Hayward had two of the Commodores' four interceptions. They have now picked off 14 passes in four games this season. The team record for a season is 24.
South Carolina smothers Vanderbilt, 21-3
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