Makeba collapsed as she was leaving the stage, the South African authorities said. She had been singing at a concert in support of Roberto Saviano, an author who has received death threats after writing about organized crime.
She died of a heart attack at the private Pineta Grande clinic in Castel Volturno near Naples in southern Italy, where she was brought by ambulance, according to a physician who spoke in return for anonymity under hospital rules.
Although Makeba had been weakened by osteoarthritis, her death stunned many in South Africa, where she stood as an enduring emblem of the travails of black people under the apartheid system of racial segregation that ended with the release from prison of Nelson Mandela in 1990 and the country's first fully democratic elections in 1994.
Widely known as "Mama Africa," she had been a prominent exiled opponent of apartheid since the South African authorities revoked her passport in 1960 and refused to allow her to return after she traveled abroad. She was prevented from attending her mother's funeral after touring in the United States.
For 31 years, Makeba lived in exile, variously in the United States, France, Guinea and Belgium. South Africa's state broadcasters banned her music after she spoke out against apartheid at the United Nations in 1976 - the year of the Soweto uprising that accelerated the demands of the black majority for democratic change.
"I never understood why I couldn't come home," Makeba said upon her return at an emotional homecoming in Johannesburg in 1990 as the apartheid system began to crumble, according to The Associated Press. "I never committed any crime."
Music was a central part of the struggle against apartheid. The South African authorities of the era exercised strict censorship of many forms of expression, while many foreign entertainers discouraged performances in South Africa in an attempt to isolate the white authorities and show their opposition to apartheid.
From exile she acted as a constant reminder of the events in her homeland as the white authorities struggled to contain or pre-empt unrest among the black majority.
Makeba wrote in 1987: "I kept my culture. I kept the music of my roots. Through my music I became this voice and image of Africa, and the people, without even realizing."
She was married several times and her husbands included the American black activist Stokely Carmichael, with whom she lived in Guinea, and the jazz trumpeter Hugh Masekela, who also spent many years in exile.
In the United States she became a star, touring with Harry Belafonte in the 1960s and winning a Grammy award with him in 1965. Such was her following and fame that she sang in 1962 at the birthday party of President John F. Kennedy. She also performed with Paul Simon on his Graceland concert in Zimbabwe in 1987.
But she fell afoul of the U.S. music industry because of her marriage to Carmichael and her decision to live in Guinea.
In one of her last interviews, in May 2008 with the British music critic Robin Denselow, she said she found her concerts in the United States . being cancelled. "It was not a ban from the government. It was a cancellation by people who felt I should not be with Stokely because he was a rebel to them. I didn't care about that. He was somebody I loved, who loved me, and it was my life," she said.
She was particularly renowned for her performances of songs such as what was known as the Click Song — named for a clicking sound in her native tongue — or "Qongoqothwane," and Pata Pata, meaning Touch Touch in Xhosa. Her style of singing was widely interpreted as a blend of black township rhythms, jazz and folk music.
In her interview in 2008, Makeba said: "I'm not a political singer. 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."