In a remarkable interview with the Evening Standard, Mr Clarke even goes as far as to say the prime minister could perhaps cite ill health for a reason for standing down.
'I think his own dignity ought to look to that kind of solution,' he said.
Mr Clarke is a well-known critic of the prime minister, but his most recent attack is particularly vicious and comes just days before the last Labour party conference before the general election.
The former home secretary said Labour faced over a decade in the wilderness if the party continued with Mr Brown as its leader.
'Are we just going to stand by and watch the whole Labour ship crash on to the rocks of May 2010 and sink for a very long time?,' he asked.
Mr Clarke also described the current team in Downing Street as 'the weakest I've ever seen in my life'.
The former ally of Tony Blair also accused those on the left of Labour of waiting for defeat in the upcoming election to claim control of the party.
'You have a kind of joint view that it's all over. That fatalism is absolutely suicidal for Labour. What makes it worse is that a lot of people in our party aren't facing up to how serious a defeat would be,' he added.
'I think we would be out for 10 to 15 years and forget what it was like for progressives during the Tory years under Margaret Thatcher.
'Those who believe there is some kind of pendulum where we go out this year and come back next are completely and utterly wrong.'
In the interview, Mr Clarke also heavily criticised the decision to allow the Lockerbie bomber to be released and returned to Libya.
'I was at the memorial service in Lockerbie and I remember it very, very vividly,' he said.
'I also met Colonel Gaddafi in his tent as home secretary and I know exactly what kind of person he is. It brings the country into disrepute when you have the president of the United States phoning up and saying it is wrong. It was a breach of faith.'
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