United look set to be without the France international for an extended period of time after he hobbled off in the second half of Saturday's 1-1 draw with Chelsea at Stamford Bridge.
Varane left the field in tears, signaling the injury could be severe, with the FIFA World Cup kicking off in Qatar in less than a month.
The 29-year-old has featured 10 times in the Premier League this season and has formed a formidable partnership with summer signing Lisandro Martinez in the heart of defence.
Speaking to FIVE YouTube channel, Ferdinand said, "Martinez has been top this season but Varane gives us that something different, that speed, that experience and physicality. I think he could be a huge loss. You need them two [Varane and Martinez] back together. We've seen straight away that those two together make us a different team, it's as simple as that."
With captain Harry Maguire currently sidelined through injury, Man United manager Erik Ten Hag opted to replace Varane with Victor Lindelof against Chelsea.
“It seems to me that it isn’t going to be Harry Maguire who comes in now. It looks like it’s going to be Lindelof,” Ferdinand added.
“Lindelof is decent, I think he will come in and do a job, it just depends how long he’s being asked to do that job.”
