The 27-year-old was taken off on a stretcher during Saturday's Barclays Premier League game against Burnley at St Mary's Stadium following an awkward fall after colliding Sam Vokes.
Scans showed damage to the player's left patellar tendon, with the usual time-frame for recovery from this type of injury between nine months and a year.
Southampton confirmed on the club's official website: "Forster will be ruled out for the rest of the season. A long-term prediction of when he will return will be made in due course."
Forster, who joined Southampton from Celtic for £10million last August, had been replaced in the England squad for the upcoming internationals by Robert Green of QPR.
Southampton's medical staff are confident the goalkeeper, who had been in good form, can make a full recovery in time.
The club's executive director of football Les Reed said: "Fraser is an outstanding goalkeeper and has been a huge part of our success this season. While this is a challenging situation, we look forward to him returning to action as soon as he is fully fit.
"I am sure he will go on to make a significant number of appearances for Southampton and for England, and will get the best support available to help him recover to do so.
"No one will be any sadder than Kelvin Davis, who did an outstanding job replacing Fraser in such circumstances. Nobody could be better to step into the fray in terms of experience and ability.
"Kelvin is a big-game player, who will be ably supported by Paulo Gazzaniga and Cody Cropper. I am sure the team will now be even more motivated to ensure we stay miserly in front of our goal and ruthless at the other end."
Southampton are in sixth place and will resume their quest for European qualification after the international break at Everton on April 4.