The marathons are intended to represent the 27 years that Mandela spent in prison, will geographically retrace the 93-year-old's life in South Africa.
"We're doing a documentary about his life, running in the areas of where he grew up," said Izzard, 50.
"Everywhere that resonates with his life, we are going to run."
The marathons, to be filmed for a documentary, will begin in the Eastern Cape, where Mandela was born and take in Pretoria, where he was on trial, and Robben Island - where he was imprisoned during the Apartheid era.
"Maybe you'll get this visceral relationship between the struggle of 27 years and the struggle of me trying to run marathons," said Izzard, who was in Johannesburg at a fundraising event for the Nelson Mandela Foundation.
All proceeds raised by the 27 marathons will be donated to the foundation and other South African charities.
'Crazy'
Izzard added that he did not expect to meet Mr Mandela during the course of the challenge
"I've already had the honour of meeting Mr Mandela... I don't want to bother him."
"If someone says to him: 'By the way, there's an idiot - you've met him before - he's doing these runs,' hopefully he might go: 'Oh, yes, running is a good idea. That is a positive thing.'
"Or he might say: 'He's crazy.'"
In 2009, the actor and comedian ran around the UK, effectively undertaking 43 marathons in 51 days, to raise money for Sport Relief.
His current challenge will be broadcast in the UK this autumn by Sky.
Comedian Eddie Izzard is to run 27 marathons in 27 consecutive days, as a tribute to the former South African president Nelson Mandela.