Izzard spoke of his plan Thursday on the sidelines of a reception for donors at Mandela's foundation and archives in Johannesburg.
He says he will run the marathons in 27 consecutive days in South Africa along routes he will map out himself at sites around the country linked to Mandela's personal history.
In 2009, Izzard ran 1,100 miles (1,770 kilometers) in seven weeks across Britain for charity.
Mandela, 93, became South Africa's first black president after its first all-race elections in 1994. He served one term, and now is retired from public life.