Tyson Fury has vacated his WBO and WBA world heavyweight titles to deal with his "medical treatment and recovery".
The Briton, 28, has admitted taking cocaine to deal with depression and could also lose his boxing licence on Thursday.
"I now enter another big challenge in my life which I know, like against Klitschko, I will conquer," Fury said.
He said it was "for the good boxing" and "only fair and right" to give up his belts.
"I won the titles in the ring and I believe that they should be lost in the ring, but I'm unable to defend at this time and I have taken the hard and emotional decision to now officially vacate my treasured world titles," he said.
In a statement, Fury's promoter Hennessy Sports said the decision would "allow him the time and space to fully recover from his present condition without any undue pressure and with the expert medical attention he requires".
Mick Hennessy added that the decision was "heartbreaking".
Uncle and trainer Peter Fury has said Fury will return "stronger" and "reclaim what's rightfully his".
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Fury withdrew from his latest rematch against Ukraine's Klitschko, scheduled for 29 October, because of mental health issues.
He then admitted in an interview with Rolling Stone magazine that he was taking cocaine to help deal with depression.
The British Boxing Board of Control (BBBofC) met on Wednesday to discuss that revelation, as well as other comments by Fury, and could decide to strip him of his licence to box.
The WBO and WBA had already said Fury could lose his titles because of inactivity.
Meanwhile, promoter Eddie Hearn has said a deal is "very close" for Britain's heavyweight champion Anthony Joshua to fight Klitschko for his IBF belt and the now vacated WBA title.
It is thought New Zealand's Joseph Parker and Mexico's Andy Ruiz Jr could now contest the WBO title.
Mike Costello, BBC Radio 5 live boxing correspondent
"First of all, Tyson Fury needs to get himself medically fit then it's up to him and his uncle and trainer Peter Fury and promoter Mick Hennessy to decide what route they want to take.
"Will he be fit enough and able enough to go straight back in for a world title shot or will he need a warm-up contest before he fights again? It's so unclear at this stage because of the medical situation."
- 29 November 2015: Beats Wladimir Klitschko to become the WBA, IBF and WBO champion
- 8 December 2015: Stripped of his IBF title for failing to fight the mandatory challenger
- 24 June 2016: Postpones July's rematch with Klitschko after injuring an ankle in training
- 4 August 2016: Charged with a doping offence by the UK's anti-doping body
- 23 September 2016: Postpones rematch for a second time because he is "medically unfit"
- 3 October: Appears to retire from boxing, tweeting: "I'm the greatest, and I'm also retired." Three hours later he reverses the decision, tweeting he is "here to stay"
- 5 October 2016: Reveals he has been taking cocaine to help him deal with depression
- 10 October 2016: Given extended deadline to convince the WBO not to strip him of his world heavyweight title
- 12 October: BBBofC meeting starts looking at Fury's boxing licence
- 12 October: Vacates WBA and WBO titles
What boxing authorities have said
WBO chairman Luis Batista-Salas had said Fury could lose his belt because of "inactivity, breach of contract and performance-enhancing drugs and stimulants".
The WBA president Gilberto Mendoza said Fury deserved a chance "to overcome this situation", but added the Englishman could ultimately lose his title.
There is an option that Fury can be declared as a 'champion in recess'. This means Fury is the mandatory challenger for the belt when he returns to the ring.
Fury is also facing a UK Anti-Doping hearing next month with reports claiming he tested positive for banned substance nandrolone in February 2015.
'None of us know what he is going through'
Trainer and uncle Peter Fury: "It's driven him to despair. I see him being back in the gym in March or April. He'll resume his career."
Billy Joe Saunders: "It is a big mistake, taking his boxing licence away. It is like taking food from a baby," he added. "He needs the licence to pull through."
IBF champion Anthony Joshua: "Tyson is a fighting man, a real talent and he is good for boxing in his own way. It's too easy to point the finger because none of us really know what he is going through."