ROME - The 76-year-old anti-apartheid activist collapsed on stage as she sang at the concert in the town of Castel Volturno, near Naples, where mafia hit men gunned down a group of African immigrants in September.
The event was organised to show solidarity with an Italian investigative journalist, Roberto Saviano, who has had death threats from mobsters for a book he wrote exposing the criminal empire of the Naples-based Camorra mafia.
Makeba was on stage when she was heard to say "I don't feel well," Italian media reported, before collapsing.
She was rushed to the private Pineta Grande Clinic in Castel Volturno, where she later died.
Her death caused deep shock and grief in her homeland. "It's a monumental loss not only to South African society in general but for humanity," said Sandile Memela, a spokesman for South Africa's Arts and Culture Ministry.
Tributes poured in on morning radio talk shows for the woman who wooed the world with her sultry voice and who was exiled from her homeland for more than three decades.
Makeba first came to international prominence when she starred in the anti-apartheid documentary Come Back, Africa in 1959.
In 1960, when she tried to fly home for her mother's funeral, she discovered her passport had been revoked. She then spent more than three decades in exile, living in the United States and Guinea.
In 1963, when she appeared before the UN Special Committee on Apartheid to call for an international boycott on South Africa, the government responded by banning her records, including hits like Pata Pata, The Click Song ("Qongqothwane" in Xhosa), and Malaika.
In 1966, Makeba received the Grammy Award for Best Folk Recording together with Harry Belafonte for An Evening With Belafonte/Makeba.
She only returned to her homeland with the crumbling of apartheid in the early 1990s.
"It was like a revival," she said. "My music having been banned for so long, that people still felt the same way about me was too much for me. I just went home and I cried."
Makeba had performed for half an hour at the concert on Sunday evening for Saviano, whose best-selling book, Gomorrah, was made into a gritty film which is currently showing in British cinemas.