It means the comic will, in total, try to run more than 700 miles in temperatures of up to 30 C.
The significance of the number 27 comes from the number of years Nelson Mandela spent in prison.
The anti-apartheid campaigner was President of South Africa from 1994 to 1999 before his death in 2013 aged 95.
Izzard said he was "delighted" to be taking on the challenge but added: "Of course, 27 marathons in 27 days is nothing compared to what Nelson Mandela did by serving 27 years in prison.
"He was a great soul and leaves a fantastic legacy for the world."
During his marathons, Izzard will explore the histories of South Africa and Nelson Mandela, as well as visiting communities, organisations and families that have all been helped by the work of Comic Relief and Sport Relief.
His journey is due to finish on 20 March when he arrives an the Union Buildings in Pretoria where Nelson Mandela gave his inaugural speech as the first democratically elected President of South Africa.
Izzard, 54, previously attempted a similar feat in South Africa in 2012, but had to pull out for health reasons.
He also completed 43 marathons in 51 days across the UK for Sport Relief in 2009, raising over Â£1.8m in the process.
Speaking about his past attempts, Izzard said: "I tried to do this four years ago and failed. This time I will succeed.
"But if I fail, I will come back again and again and again until I do succeed. Because that's what Nelson Mandela would have done."
The marathons will be covered on BBC Three, which is about to move from television to online.
Sport Relief raises money for disadvantaged people in some of the world's poorest communities.
It takes place every two years, alternating with Red Nose Day.

Taking place in Northern Ireland for the first time, this year's event is live at The SSE Arena on 20 December.
Gary Lineker, Clare Balding and Gabby Logan will again present the show, which will be live on BBC One, the BBC Sport website and BBC Radio 5 live.
A limited number of extra tickets will be available closer to the event.
Carl Doran, the show's executive editor, said: "We are delighted that tickets for Sports Personality of the Year 2015 in Belfast have sold out so quickly.
"It's testament to the appeal of the show and for those who got tickets or choose to watch on BBC One, it's going to be a great evening of entertainment."
Logan added: "This has been a brilliant year for sport and we're all very much looking forward to celebrating it in Belfast.
"Sports Personality is always a great show and having had a sneak peek at this year's plans, it looks like the event is going to be one of the best yet."
The Sports Personality of the Year award will be determined by a public vote on the night with the 10-strong list of contenders selected by the following panel:
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Formula 1 world champion Lewis Hamilton won last year's Sports Personality of the Year award in Glasgow, taking 34% of the 620,932 votes cast, with golfer Rory McIlroy second and athlete Jo Pavey third.
Real Madrid footballer Cristiano Ronaldo was named Overseas Personality of the Year, and the England women's rugby union team took the Team of the Year prize.
European Ryder Cup captain Paul McGinley won Coach of the Year, six-time Olympic gold medallist Sir Chris Hoy was honoured with a lifetime achievement award, and Young Sports Personality of the Year was given to gymnast Claudia Fragapane, who won four gold medals at the 2014 Commonwealth Games.
This year's highpoints include both Northern Ireland and Wales reaching their first major football tournaments in decades, cyclist Chris Froome claiming his second yellow jersey in the Tour de France and England finishing third in the Women's World Cup.
Then there was Wayne Rooney becoming the Three Lions' top goalscorer, Great Britain reaching their first Davis Cup final since 1978, England's Ashes triumph and a Rugby World Cup taking place on British soil.
And let's not forget swimmer Adam Peaty setting a new world record at the World Swimming Championships, Hamilton's continued excellence in Formula 1, and Mo Farah, Jessica Ennis-Hill and Greg Rutherford all winning gold medals at the World Athletics Championships.
Sports Personality Roll of Honour: Every winner from 1954-2014
Eddie Izzard will attempt to run 27 marathons in 27 days through South Africa for Sport Relief, the BBC has announced.
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Tickets for BBC Sports Personality of the Year 2015 in Belfast sold out in 35 minutes - the quickest sell-out since the show went on the road in 2006.