Tsvangirai died of complications from cancer at a hospital in Johannesburg, South Africa, surrounded by family, his wife Elizabeth Tsvangirai confirmed.
"We are all heartbroken. It is terrible, The legacy of Tsvangirai is that he was one of the greatest opposition leaders of the post colonial period, and he defeated one of the major liberation movements of the region, and he was denied that victory," Zimbabwe's veteran analyst and academic, Brian Raftopoulos said. "He was beaten, tortured, imprisoned, exiled and yet he still retained a real basic humanity and a wonderful sense of humour. Tsvangirai was a really warm human being."
Tsvangirai was born March 10, 1952, in the Gutu area of Southern Rhodesia and joined Mugabe's Zanu-PF Party when Zimbabwe gained independence in 1980, after serving as an executive of the National Mine Workers Union.
He later rose to become head of the Zimbabwe Congress of Trade Unions and as congress severed ties with Zanu-PF, Tsvangirai led a series of strikes in late 1997 and early 1998.
In 1999 Tsvangirai founded the Movement for Democratic Change which became a political force in the 2000 election, challenging Zanu-PF's 62 constituency-based seats by winning 57.
Tsvangirai was arrested shortly after the election as a threat to Mugabe's government. He also was arrested in 2003 for accusing Mugabe of using violence and intimidation to remain in power.
He sustained a fractured skull and internal bleeding after he was arrested in 2007 and taken to a special forces barracks where he was badly beaten.
After running in a tightly contested election against Mugabe in 2008, Tsvangirai pulled out of the second round voting, stating a free and fair vote was impossible as his supporters faced violence and imprisonment at the hands of Mugabe's security forces.
South Africa helped broker a power-sharing deal and Tsvangirai was sworn in as prime minister in February 2009.
Tsvangirai was criticized for dropping out of the election as Mugabe maintained control over the government and he ultimately resigned as prime minister after the MDC party faced defeat in the 2013 elections.
People in central Harare publicly wept at the news of Tsvangirai's death and Zimbabwe historian David Moore said he will be remembered for his bravery.
"Tsvangirai, changed the lives and expectations of ordinary people as Robert Mugabe made it clear, from independence, he was committed to a one-party state," Moore said. "No one in Zimbabwe's sad history did more to challenge the fearful state created by Mugabe, then Tsvangirai."