Jail, beatings by pro-regime thugs and perennial disappointment at the ballot box never dented the 65-year-old's desire to move the country past the decades of autocratic rule by former president Robert Mugabe and his acolytes.
The leader of the opposition Movement for Democratic Change party (MDC) took his furtive first steps on the country's complex and sometimes violent political scene as a trade union activist in the 1980s.
He went on to form a unity government with Mugabe after disputed elections in 2008 in which he beat the veteran autocrat -- now 93 years old -- in the first round of the vote.
But violence against Tsvangirai's supporters, which he claimed cost 200 lives, prompted him to pull out of the run-off.
Only outside mediation helped put the lid back on Zimbabwe's fractious politics and usher in a period of power sharing and relative calm.
But Tsvangirai was quickly relegated to junior partner in the coalition and excluded from all major economic and foreign policy decisions, as well as from any debate over the role of the security services.
He faced off against Mugabe three times at the ballot box and had been expected to oppose him once again in presidential elections set for 2018.
"ZANU-PF has not won recent elections, it has rigged them," Tsvangirai told AFP previously.
"Anyone who is interested in ending ZANU-PF should unite, in spite of ideological differences."
A teetotalling non-smoker from Zimbabwe's majority Shona community, Tsvangirai had widely been seen as the best hope for reviving Zimbabwe's divided politics and moribund economy and was a forceful anti-corruption advocate.
Mugabe's government detained him on numerous occasions over his vocal criticism of the regime.
Security forces swooped on Tsvangirai in 1989 after he bluntly warned about the rising tide of political repression in the country.
Tsvangirai also claimed to have been the target of four assassination attempts -- including one in 1997 in which he said attackers attempted to throw him out of his office window.
His political career almost ground to a halt in 2001 when he was tried over allegations he had conspired to kill Mugabe, levelled by a self-proclaimed ex-Israeli spy. Tsvangirai was eventually cleared.
In March 2007, police violently cracked down on Tsvangirai and dozens of opposition activists when they attempted to stage an anti-government rally.
Images of his bloody, mangled face were seen worldwide, leading to global condemnation of Mugabe and his security forces.
"Yes, they brutalised my flesh. But they will never break my spirit. I will soldier on until Zimbabwe is free," he said at the time.
Tsvangirai was recognised on several occasions for his commitment to political change, and was widely thought to have been shortlisted for the Nobel Peace Prize in 2008, 2009 and 2010.
In 2009, just three weeks after becoming prime minister in Zimbabwe's first post-independence power-sharing government, his wife Susan was killed in a car crash that also left him injured.
But some commentators suggested that it was his crushing defeat in fraud-riddled elections in 2013 that he was never able to recover from.
And in 2016 he announced that he was undergoing chemotherapy to treat colon cancer.
Tsvangirai surprised many by outlasting Mugabe in active public life after the former president was eased from power following a military takeover that saw Mugabe's former deputy Emmerson Mnangagwa become president.
Tsvangirai and Mnangagwa enjoyed a cordial relationship with the opposition veteran attending the new president's inauguration.
Born in 1952 in Gutu, a remote farming area south of the capital Harare, Tsvangirai was the eldest of nine children whose father worked as a bricklayer.
He grew up in the eastern Buhera region and was forced by poverty to leave school early and start work as a trainee weaver so that his siblings could continue with their studies.
After working as a weaver for two years he became a foreman at a nickel mine in Mashonaland, northern Zimbabwe, where he would stay for 10 years until taking the plunge and becoming a trade unionist.
Unlike most of Zimbabwe's leading politicians, Tsvangirai did not fight in the liberation war against Britain despite being 28-years-old when Zimbabwe won its independence.
He did join the ZANU-PF, but left after becoming disillusioned with the party's direction.
In 1988 he was elected secretary general of what later became the Zimbabwe Congress of Trade Unions.
Tsvangirai emerged as a powerful political force in December 1997 when he led the Zimbabwe Congress of Trade Unions in crippling strikes over the rising cost of living which brought the country to a standstill.
An eloquent and persuasive speaker, he kept up the pressure even after the strike was ended as Zimbabwe's economic woes worsened.
In 1999 he created the MDC in a bid to end Mugabe's grip on power, firmly held since independence in 1980 until November 2017.
Tsvangirai's critics argued that his commitment to contesting elections and a willingness to share power allowed Mugabe to cling to office.
But to his supporters he sacrificed personal gain to stabilise Zimbabwe when its economic and political prospects were at their lowest, ushering in an era of relative calm.
- Countries: Africa