Mr de Klerk, who was also a key figure in the nation’s transition to democracy, had been diagnosed with cancer this year, a spokesman said.
Mr de Klerk was head of state between September 1989 and May 1994.
In 1990 he announced he was releasing anti-apartheid leader Nelson Mandela, leading to multi-party polls in 1994.
A statement from the former president’s FW de Klerk Foundation on Thursday morning read: “Former President FW de Klerk died peacefully at his home in Fresnaye (Cape Town) earlier this morning following his struggle against mesothelioma cancer.”
The foundation had announced the diagnosis – a cancer that affects the lining of the lungs – in June this year.
FW de Klerk had taken over from PW Botha as the head of the National Party in February 1989 and the following year announced he was removing the ban on parties that included Mr Mandela’s African National Congress (ANC).
His actions helped bring an end to apartheid-era South Africa, and he became one of the country’s two deputy presidents after the multi-party elections in 1994 that saw Mr Mandela become president.
He shared the Nobel Peace Prize with Mr Mandela in 1993.
However, his role in the transition to democracy was always highly contested. Last year, he became embroiled in a row in which he was accused of playing down the seriousness of apartheid. He later apologised for “quibbling” over the matter.