The Springboks will now look likely to play the loser of Saturday's Australia-Wales Group B game in Cardiff in the quarterfinals, while England still has to beat Tonga and Samoa to advance to the last eight as runner-up.
"We've got to get over this game first and we've got an incredibly tough match against Samoa coming up," said stand in captain Martin Corry.
"Of course we're going to be ready for it. We'll get over this defeat and do all we have to do to be ready for Samoa."
Flanker Juan Smith also scored and fullback Percy Montgomery had 18 points.
Scrumhalf Fourie du Preez gave England a lesson in organisational rugby as he set up all three tries, directing his forwards and constantly threatening England's defence.
With first-choice flyhalves Jonny Wilkinson and Olly Barkley out injured, England's lack of a kicking game had them playing out of their own half for most of the game.
"We're very disappointed about the game and the performance. Early on, we gave them opportunities to score and they took them," said Corry.
"They showed great finishing expertise but we gave them those opportunities."
While South Africa had a superior kicking game, it was Du Preez's running game that created the opening try after just six minutes.
His pass allowed Pietersen to beat England No. 9 Shaun Perry down the short side and race into the England 22.
The flying winger then fed the ball back to Du Preez, who found Smith in support to cross untouched.
Montgomery, who equalled former scrumhalf Joost van der Westhuizen for most South African test appearances at 89, converted for 7-0.
A penalty by No. 12 Francois Steyn in the 11th extended the lead.
It was simply all South Africa and after Montgomery kicked another penalty, it soon got worse for the 2003 world champions.
Du Preez pounced on a loose ball and in broken play had a 3-on-1 overlap on the right flank as he streaked into England territory.
He drew the stranded Jason Robinson and Pietersen raced over to score in the 38th as South Africa took a 20-0 halftime lead.
Montgomery kicked two penalties after the break to take the match further away from England.
The game was now out of reach, but if England thought it couldn't get any worse, they were wrong.
Their remaining chances in the tournament were struck a further blow when Robinson, easily England's best player, left the field in the 58th with a left hamstring injury.
In the 64th, Du Preez set up the third try, Pietersen's second, when he ran around England's lagging defenders on the fringes and passed for the Springbok winger to score on the right flank.
Montgomery landed his seventh straight kick and then a final penalty to complete the whitewash.