The 38-year-old Dutchman sustained the injury saving a penalty from Danijel Pranjic in Manchester United's 7-6 shoot-out defeat to Bayern Munich in the pre-season Audi Cup in Germany.
Van der Sar is not expected to be back in Sir Alex Ferguson's plans until late September, meaning the Scot will have to turn to either Ben Foster or Tomasz Kuszczak between the posts for the start of the new season.
His absence opens the way for Foster to prove himself as Ferguson's first choice in goal.
Despite being heralded by his manager as England's best goalkeeper, the 26 year-old has been limited at Old Trafford through injuries and Van der Sar's consistency.
Last week Ray Clemence warned Foster he must be playing regularly this season to be considered part of Fabio Capello's World Cup plans.
Foster only has two England caps to his name but has been tipped by Ferguson to claim the England No 1 jersey for next year's World Cup in South Africa.
Clemence said: "To play international football you need to be playing games on a regular basis and that is his target this year: to get the opportunity to play consistently in the team.
"Then what he has to do is take that opportunity and say, 'Sorry Edwin, you're not having your place back'."
Foster, who has played only 10 times for Manchester United, signed a new four-year contract at Old Trafford this summer.
Van der Sar's injury will be a major blow for Ferguson, who already needs to decide whether he has the men to replace Scholes, Ryan Giggs, Gary Neville and Van der Sar, all of whom could be retiring at the season's end.