The Pineta Grande Clinic, a private clinic near the southern city of Naples, said the singer died after being brought there. The ANSA news agency reported that Makeba apparently suffered a heart attack after performing for 30 minutes at a concert against organized crime.
The death of "Mama Afrika," as she was known, plunged South Africa into shock and mourning.
"One of the greatest songstresses of our time has ceased to sing," Foreign Affairs minister Nkosazana Dlamini Zuma said in a statement.
"Throughout her life, Mama Makeba communicated a positive message to the world about the struggle of the people of South Africa and the certainty of victory over the dark forces of apartheid and colonialism through the art of song."
Makeba wrote in her 1987 memoirs that friends and relatives who first encouraged her to perform compared her voice to that of a nightingale. With her distinctive style combining jazz with folk with South African township rhythms, she was often called "The Empress of African Song."
She first started singing in Sophiatown, a cosmopolitan neighborhood of Johannesburg that was a cultural hotspot in the 1950s before its black residents were forcibly removed by the apartheid government.
She then teamed up with South African jazz trumpeter Hugh Masekela -- later her first husband -- and her rise to international prominence started when she starred in the anti-apartheid documentary "Come Back, Africa" in 1959.
When she tried to fly home for her mother's funeral the following year, she discovered her passport had been revoked. It was 30 years before she was allowed to return.
In 1963, Makeba appeared before the U.N. Special Committee on Apartheid to call for an international boycott of South Africa. The South African government responded by banning her records, including hits like "Pata Pata," "The Click Song" ("Qongqothwane" in Xhosa), and "Malaika."
Makeba received the Grammy Award for Best Folk Recording in 1966 together with Harry Belafonte for "An Evening With Belafonte/Makeba." The album dealt with the political plight of black South Africans under apartheid....
Rest in peace in the choir of angels.