The Springboks were simply too powerful, though the Scots put on brave second-half performance which at one stage raised hopes of a thrilling comeback in Newcastle's St. James' Park.
South Africa, upset 34-32 by Japan in their first game, dominated the first half and tries by flanker Schalk Burger and winger JP Pietersen gave them a 20-3 lead at the interval.
Scotland fought back with a fine try by winger Tommy Seymour after an interception but the reliable boot of South Africa flyhalf Handre Pollard kept his team in control of the match.
Winger Bryan Habana's late try applied gloss to the South Africa win and they top Pool B ahead of their final group match against the United States.
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South Africa coach Heyneke Meyer expressed relief that the Springboks had put their poor start to the tournament behind them.
"I thank the Lord for being with us. It's been a tough two weeks," he told reporters.
"In the second half we lost momentum. But you have to give credit to Scotland. We knew this was a must-win."
In the early stages, the Springboks, playing in white instead of their famed dark green, attacking in waves.
It took consultation with the television match official before referee Nigel Owens awarded the first try, Burger adjudged to have grounded the ball amid a pile of bodies.
On the rare occasions when Scotland pushed into the Boks half, the South Africans smothered them, backs Willie le Roux and Pietersen always looking dangerous and ready to break out.
A Greig Laidlaw penalty kept Scotland in touch but Pietersen jinked over for a try following a lineout.
The Scots had a mountain to climb but came out for the second half with purpose, a Laidlaw penalty lifting spirits.
South Africa assaulted the Scottish line again and just when it seemed another try was coming, Duncan Weir picked up a loose pass and scampered the length of the field before finding Seymour in support to go over for the try.
A Pollard drop goal followed to give the South Africans breathing space and though Scotland running flair and pulled it back to 23-16 with a Weir penalty, another Pollard penalty kept South Africans clear and Habana's try added a final flourish.
"After their try we were under pressure again. (The drop kick decision) wasn't anything said. It was just a look in the eye." South Africa captain Fourie du Preez told reporters.
Scotland coach Vern Cotter said the score was a fair reflection of the game.
"They dominated in their contact area and we struggled to move forward," he said. "In the second half the players stepped up."
Scotland, second in the Pool B table, take on Samoa next Saturday with victory set to secure qualification.
South Africa face the United States on Wednesday.
(Editing by David Goodman)
