The Kathrada Foundation confirmed that the 87-year-old passed away at the Donald Gordon Hospital on Tuesday morning.
Kathrada's health deteriorated on Monday after he was admitted to hospital for surgery related to blood clotting in the brain earlier this month.
His condition worsened in the past 24 hours due to pneumonia which developed after the operation.
Kathrada will be buried according to Muslim religious rights, details of which will be made publicly available in due course.
Kathrada was born in the North West town of Schweizer-Reneke in 1929.
He began his political career at the tender age of 17, leading to numerous incidents of incarceration before and after he joined the African National Congress (ANC).
Alongside seven others, which includes former President Nelson Mandela, Walter Sisulu and Govan Mbeki, Kathrada stood trial after he was arrested in a police raid on a meeting at the Liliesleaf Farm in Rivonia.