Richard Moore, 59, was pronounced dead at 6.24pm after receiving a lethal injection at a prison in state capital Columbia, media witnesses said.
Governor Henry McMaster declined to issue a last-minute grant of clemency.
Moore was sentenced to death in 2001 for the 1999 killing of James Mahoney, a white convenience store clerk, during what prosecutors said was a robbery attempt.
Moore’s lawyers deny he ever planned to rob the store.
He entered the store unarmed, they said, but got into an argument with Mahoney because he was 11 or 12 cents short of the money needed to make his purchase.
Mahoney allegedly pulled out two guns and Moore wrestled one away, shooting the store clerk to death while being wounded in the arm himself.
According to prosecutors, Moore stole US$1,400 and went out to buy crack cocaine.
He was arrested soon afterwards.
Moore’s lawyers said his death sentence was unfair and racially motivated.
“No other South Carolina death penalty case has involved an unarmed defendant who defended himself when the victim threatened him with a weapon,” they said in a statement.
“Moore is not the ‘worst of the worst’ for whom the death penalty is supposed to be reserved,” they added.
“Instead, his death sentence is based on racial discrimination.”
The prosecutor “had a history of seeking the death penalty only in cases involving white victims”, Moore’s lawyers said, and rejected all of the potential African-American jurors during jury selection.
The US Supreme Court on Thursday declined Moore’s request for a stay of execution.
Those seeking clemency for Moore included Jon Ozmint, the former director of the South Carolina department of corrections.
“He’s a changed man,” Ozmint said in a video.
“There’s no question in my mind this would not have been a death penalty case in most states.”
Moore also appeared in the clemency video, saying: “I hate that it happened. I wish I could go back and change it. I took someone’s life. I broke the family of the deceased.”
There have been 21 executions in the US this year, with Moore the second condemned prisoner put to death in South Carolina.
The death penalty has been abolished in 23 of the 50 US states, while six others – Arizona, California, Ohio, Oregon, Pennsylvania and Tennessee – have moratoriums in place.