The Grammy-nominated singer, sometimes called the "White Zulu", died peacefully at home in Johannesburg on Tuesday with his family, according to Clegg's manager, Roddy Quin.
Clegg, who was very outspoken about apartheid in the 1980s, sold more than five million albums over three decades and enjoyed a massive following worldwide, especially in France, where he was fondly known as "the white Zulu".
The South African government and fellow musicians paid tribute to Clegg as a musician and an activist.
On its official Twitter page, South Africa's government paid tribute to Clegg's achievements.
He authored and published the book "UkuBuyisa Isidumbu" (1981, Ravan Press), and presented papers on "The Music of Zulu Immigrant Workers in Johannesburg" in 1981 at the Grahamstown International Library of African Music and "Towards an understanding of African Dance: The Zulu Isishameni Style" in 1982 at Rhodes University.
The fall of apartheid in 1994 was like a rebirth for South Africans, Clegg said in a 2002 interview, and brought new challenges.
His song "Asimbonanga" was dedicated to Mandela and released in 1987, when the future first black president of South Africa was still jailed as a threat to the apartheid state. His love for South Africa, the people and the languages reflected in all his music.
In what Clegg said was a highlight of his career, Mandela made a surprise entrance on stage during a performance of the hit in Frankfurt in 1999. He was just fantastic. I travelled to NY with Jesse Clegg, it's just fantastic family.
In late 2017, he embarked on a farewell tour called The Final Journey that took him to 12 cities in North America before circling back to Africa.
Johnny was diagnosed with pancreatic cancer in 2015 but despite fighting cancer continued to tour and perform around the world to pay homage to his fans worldwide.
"It has been a rewarding career in so many aspects.to be able to unite people through song, especially at a time where it seemed impossible", he said.
Johnny is survived by his wife of 31 years, Jenny and their two sons Jesse and Jaron.