Uncapped Tottenham defender Michael Dawson will fly to South Africa to replace Ferdinand while Steven Gerrard will take over as captain.
England captain Rio Ferdinand was ruled out of the World Cup on Friday after injuring his left knee in the team's first full training session since arriving in South Africa.
The 31-year-old central defender suffered a ligament injury in the final minutes of training after he went into a tackle and fell badly.
Liverpool's Steven Gerrard will now captain the team, the Football Association said in a statement.
"Further to a scan arranged by the England medical staff immediately after training on Friday afternoon, Rio has been ruled out for four to six weeks and will therefore, unfortunately, miss the World Cup," the FA said.
Tottenham Hotspur's Michael Dawson is to fly to South Africa to take Ferdinand's place in the 23-member squad.
England manager Fabio Capello said: "It is obviously bad news and everyone with the squad is very disappointed and sorry for Rio.
"It was an accidental injury in training but had nothing to do with the pitch."
The Italian also said goalkeeper David James had missed training owing to a nagging knee injury aggravated by the long flight from London.
There was some consolation for the beleaguered England camp with better news over midfielder Gareth Barry's injured right ankle.
"He is getting better and better every day. He started training with the team. He will go to the gym this afternoon with the physiotherapist and always train with the team in the mornings," Capello said.
The manager, though, was unsure if Barry would feature in England's opening match against the United States on June 12.
"He will not do everything just yet and we have to be a little careful with him just at this moment," said Capello.
Ferdinand took over as captain after Chelsea's John Terry was stripped of the job in February because of an off-pitch scandal involving his private life, but he has not played regularly for Manchester United this season owing to a succession of injuries.
The United defender appeared for England in the 2002 and 2006 World Cups and has made a total of 78 appearances, scoring three goals.
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