Tsvangirai was born in the Buhera area, in then Southern Rhodesia, to Karanga Shona parentage through his father Dzingirai-Chibwe Tsvangirai and mother Lydia Tsvangirai (née Zvaipa). He was the eldest of nine children, and the son of a communal farmer, mine worker, carpenter and bricklayer. He completed his primary education at St. Marks Goneso Primary School Hwedza, and was transferred by his father to Chikara Primary School Gutu, then to Silveira. He completed his secondary education at Gokomere High School. After leaving school with 8 Ordinary levels, in April 1972 he landed his first job as a trainee weaver for Elastics & Tapes textile factory in Mutare. In 1974 an old school mate from Silveira encouraged Morgan to apply for an advertised job as an apprentice for Anglo America's Bindura's Nickel Mine in Mashonaland Central. He spent ten years at the mine, rising from plant operator to plant supervisor. His rural home was Buhera, which is 220 km south east of Harare.

Tsvangirai married his first wife, Susan, in 1978. The couple had six children during their 31-year marriage, which ended with her death in the 2009 car crash. In 2011 Locardia Karimatsenga (born 1970) claimed that Tsvangirai married her in a customary ceremony in 2010. She had been seeking maintenance payments of £10,000 a month to keep up the lifestyle to which, she said in court papers, she had become accustomed. A year later, his love life made headlines again after a 23-year-old woman bore him a child and he refused to support the baby until she threatened to take him to court. He married his second wife, Elizabeth Macheka (born 1976) mother of three, on 15 September 2012.

Upon Zimbabwean independence in 1980, Tsvangirai, who was then aged 28, joined the ascendent ZANU–PF party, led by Robert Mugabe, who would later become his biggest political rival. Tsvangirai is reported to have been an ardent Mugabe supporter and to have risen "swiftly in the hierarchy", eventually becoming one of the party's senior officials. He is also known for his role in the Zimbabwean trade union movement, where he held the position of branch chairman of the Associated Mine Workers' Union and was later elected into the executive of the National Mine Workers' Union. In 1989 he became the Secretary-General of the Zimbabwe Congress of Trade Unions, the umbrella trade union organisation of Zimbabwe.

Tsvangirai led the ZCTU away from the ruling ZANU-PF. As his power and that of the movement grew, his relationship with the government deteriorated.

Three years after coming to power, Robert Mugabe ordered the 5th Brigade, a military unit specially trained by North Korea, to commit a massacre in Matabeleland in co-operation with the Minister of Defence Enos Nkala, led by Air Marshal Perrance Shiri because of suspicion of an alleged counter-revolution being planned by Joshua Nkomo. Tsvangirai would later use Gukurahundi against ZANU and to drum up support in Matabeleland. Tsvangirai has periodically toured the mass graves of the victims in Tsholotsho, Kezi, Lupane, Nkayi and other places in rural Matabeleland. Addressing villagers in Maphisa in 2001, he said:

This was a barbaric operation by ZANU-PF. It should never have happened. It was a sad episode in our history and the MDC will obviously want to see justice being done if it comes to power. Such human rights abuses should be revisited and those responsible will have to account for their actions.

The National Constitutional Assembly (NCA), established in 1997, was chaired by a Moderator, and its day-to-day executive was run by a Task Force. Tsvangirai chaired the Task Force, as founding convener Tawanda Mutasah (succeeded by Bishop Nemapare) served as Moderator. Serving with Tsvangirai in the Task Force were activists that included Lovemore Madhuku, Welshman Ncube, Everjoice Win, Brian Kagoro, Tendai Biti and Priscilla Misihairabwi. The NCA gathered individual Zimbabwean citizens and civic organisations including labour movements, student and youth groups, women's groups, churches, business groups and human rights organisations. These individuals and groups formed the NCA to campaign for constitutional reform after realising that the political, social and economic problems affecting Zimbabwe were mainly a result of the defective Lancaster House constitution and could only be resolved through a new and democratic constitution. Tsvangirai stepped down after being elected president of the MDC.