The decision to go under the knife came following an extensive consultation period and will rule the 23-year-old out of key Champions League group fixtures and the club's busy Christmas fixture schedule.
"Following consultation with several independent ankle specialists, it has been determined that Tom Huddlestone will undergo surgery on his right ankle," read a statement on the club's website.
"The procedure is likely to rule the England international out of action for around three months."
Huddlestone has been a virtual ever-present this season but in recent weeks had seen his game time rationed due to the ankle problem, which has required a series of injections.
The former Derby midfielder joins a growing injury list at White Hart Lane, which has already left Redknapp without the likes of Ledley King, Michael Dawson, Jermain Defoe, Jonathan Woodgate, Aaron Lennon, Jamie O'Hara and Robbie Keane.
The loss of Huddlestone comes amid the build-up to this weekend's north London derby against Arsenal at the Emirates Stadium. The injury also rules him out of high-profile Premier League games with Chelsea, Liverpool and Manchester United.
In addition, Huddlestone will be absent from two key European games against Werder Bremen and FC Twente in the coming weeks, with a place in the knockout stages of the Champions League at stake.
Should Spurs progress to the last 16, Huddlestone would be hopeful of featuring, with those fixtures due to begin in mid-February.
Tottenham assistant manager Kevin Bond admitted the loss of Huddlestone was a blow but was confident the depth of the squad could cover his absence.
"It looks like he's going to have to have a little clean-out of the ankle and it looks like he's going to be out for some time," Bond told Sky Sports News.
"He's been excellent for us for some time now, but that's what we've got the squad for.
"Jermaine Jenas played central midfield on Saturday and was brilliant, so we've got a squad of players and they've all got to play their part. They'll certainly have to do that because we'll be without Tom for a good while.
"There's a lot good players in our squad; we've got no problems with playing any of our players.
"You'd like to be able to pick from a full squad obviously, but at this moment in time we're not able to do that."