In her dazzling career, Makeba performed with musical legends from around the world - jazz maestros Nina Simone and Dizzy Gillespie, Harry Belafonte, Paul Simon - and sang for world leaders such as John F. Kennedy and Nelson Mandela.
Her distinctive style, which combined jazz, folk and South African township rhythms, managed to get her banned from South Africa for over 30 years.
"Her haunting melodies gave voice to the pain of exile and dislocation which she felt for 31 long years. At the same time, her music inspired a powerful sense of hope in all of us," Mandela said in a statement.
He said it was "fitting" that her last moments were spent on stage.
Makeba collapsed after singing one of her most famous hits "Pata Pata," her family said. Her grandson, Nelson Lumumba Lee, was with her as well as her longtime friend, Italian promoter Roberto Meglioli.
"Whilst this great lady was alive she would say: 'I will sing until the last day of my life'," the family statement said.
Makeba died at the Pineta Grande clinic in Castel Volturno, near the southern city of Naples, after singing at a concert in solidarity with six immigrants from Ghana who were shot to death in September in the town. Investigators have blamed the attack on organized crime.
The death of "Mama Africa" sent shock waves through South Africa, where callers flooded local radio stations with their recollections of her. In Guinea, where Makeba lived most of her decades in exile, radio and television stations played mournful music and tributes to their adopted icon.
The first African to win a Grammy award, Makeba 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 in 1959 when she starred in the anti-apartheid documentary "Come Back, Africa."
When she tried to fly home for her mother's funeral the following year, she discovered her passport had been revoked.
In 1963, Makeba appeared before the U.N. Special Committee on Apartheid to call for an international boycott of South Africa. The white-led 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 Belafonte for "An Evening With Belafonte/Makeba."
The album dealt with the political plight of black South Africans under apartheid.
Thanks to her close relationship with Belafonte, she received star status in the United States and performed for President Kennedy at his birthday party in 1962. But she fell briefly out of favor when she married black power activist Stokely Carmichael - later known as Kwame Ture - and moved to Guinea in the late 1960s.
Besides working with Simone and Gillespie, she also appeared with Paul Simon at his "Graceland" concert in Zimbabwe in 1987.
After three decades abroad, Makeba was invited back to South Africa by Mandela shortly after his release from prison in 1990 as white racist rule crumbled.
"It was like a revival," she said about going home. "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."
Tributes flooded in Monday from across Africa.
Congo's minister of culture, Esdras Kambale, called Makeba a role model for all Africans.
"We are very saddened," Kambale said. "Fortunately, she left a large body of music that will be immortal."
Percussionist Papa Kouyate - who played in Makeba's band for 20 years and is the widower of her daughter Bongi - remembered Makeba as a giving person.
"I married her daughter Bongi and she adopted me as her own child," he said. "I will mourn Mama Africa for a long time."
Still, Makeba attracted controversy by lending support to dictators such as Togo's Gnassingbe Eyadema and Felix Houphouet-Boigny from Ivory Coast, performing at political campaigns for them even as they violently suppressed democratic movements in West Africa in the early 90s.
The first person to give her refuge was Guinea's former President Ahmed Sekou Toure, who has been accused in the slaughtering of 10 percent of his country's population.
Makeba insisted, however, that her songs were not deliberately political.
"I'm not a political singer," she insisted in an interview with Britain's Guardian newspaper earlier this year. "I don't know what the word means. People think I consciously decided to tell the world what was happening in South Africa. No! I was singing about my life, and in South Africa we always sang about what was happening to us - especially the things that hurt us."
Makeba announced her retirement three years ago, but despite a series of farewell concerts she never stopped performing. When she turned 75 last year, she said she would sing for as long as possible.
Makeba is survived by her grandchildren, Nelson Lumumba Lee and Zenzi Monique Lee, and her great-grandchildren Lindelani, Ayanda and Kwame. A funeral will be held in South Africa, but details have not yet been announced.
Photographer Jurgen Schadeberg, who shot widely acclaimed pictures of Makeba for Drum magazine in the 50s, felt she epitomized the era where politics and culture collided in a heady mix.
"We are losing our great divas," he lamented by telephone from France.
