Earlier this month Tsvangirai was reported to be critically ill in hospital. He had reportedly been suffering from colon cancer.
Morgan Tsvangirai, Zimbabwe's longtime opposition leader and political rival of former Prime Minister Robert Mugabe, has died at 65.
His death was confirmed to Reuters by a member of his Movement for Democratic Change (MDC) party.
Earlier this month, it was reported he was critically ill in a hospital in South Africa. He had reportedly been suffering from colon cancer.
MDC Vice President Elias Mudzuri tweeted the party had "lost our icon and fighter for democracy."
Tsvangirai founded the MDC party in 1999, and was a key opposition figure during Robert Mugabe's 37-year hold on power.
BBC News' Africa Editor Joseph Winter wrote a tribute to Tsvangirai saying he was an "incredibly brave man who risked his life to stand up to the authoritarian rule of Robert Mugabe."
Tsvangirai was the eldest of nine children, and spent his early years as a textile worker and miner.
After the country's independance in 1980, Tsvangirai joined the patriotic ZANU-PF party, led by future rival Robert Mugabe.
In 1989, he became secretary general of Zimbabwe's Congress of Trade Unions, before creating the MDC party and leading the opposition against Mugabe.
According to Reuters, Tsvangirai was arguably Zimbabwe's most popular politician, defined by his years-long conflict with the former-president. He went on to form a tense working relationship with Mugabe in 2009, working briefly as the country's Prime Minister, as part of the country's coalition government.
Tsvangirai challenged Mugabe again in 2013 but lost, claiming election fraud.
According to the BBC, the MDC is now divided on who will lead the opposition party in elections later this year.