Spurs' fears over the injury the striker suffered in England's European Championship qualifier in Switzerland on Tuesday night were confirmed following consultation with a specialist on Thursday.
It means the 27-year-old could miss all of his club's Champions League group matches, as well as two England internationals.
A statement on Spurs' official website read: "Following a review by an ankle specialist, Jermain Defoe underwent surgery to repair torn ligaments in his right ankle yesterday evening.
"The striker was forced off with the injury during England's European Championship qualifier in Switzerland on Tuesday and has been ruled out of action for around three months."
Defoe had been confident immediately after Tuesday night's game that the injury which saw him carried off on a stretcher was not serious and that he could even be fit for his club's Premier League game at West Brom.
But he was on crutches at Spurs' training ground on Thursday and was wearing a protective boot on his right ankle, with manager Harry Redknapp confirming he would be out for a minimum of six weeks.
But the problem appears to have been even more serious than the injury suffered by team-mate Michael Dawson during England's win over Bulgaria on Friday night.
Dawson escaped with sprained ankle and knee ligaments, despite his left leg collapsing freakishly beneath him, and was told he would be out for up to eight weeks.
The absence of two key players is a huge blow for Spurs' ambitions of progressing from their Champions League group in what is their first season in the competition.
It is also a setback for England boss Fabio Capello, who will need to rethink his plans for next month's Euro 2012 qualifier against Montenegro and possibly November's friendly with France.