His death is a huge blow to the opposition in Zimbabwe and comes just months before the first elections in former British colony since the end of Robert Mugabe’s near four-decade rule last year.
Mr Tsvangirai’s illness, revealed in 2016, has divided his Movement for Democratic Change (MDC) party, with three deputy leaders and other officials publicly manoeuvring to succeed the former trade union leader.
The party will have to choose a new leader and launch a campaign against a resurgent Zanu-PF, the ruling party, to contest polls that may be held as early as May.
Mr Tsvangirai was one of Zimbabwe’s most popular politicians and came close to unseating Robert Mugabe, only to be outmanoeuvred and ultimately outlived by his bitter rival.
At the peak of his career, the self-taught son of a bricklayer served as prime minister to Mr Mugabe’s president in a 2009-2013 unity government cobbled together after a disputed and violent election in which scores of his supporters were killed.
His presence helped stabilise an economy in freefall but Mr Mugabe went back on promises to overhaul the country’s partisan security forces and Mr Tsvangirai was pushed back into his familiar role in opposition.