Edwin Thabo Mofutsanyana was born in the Witzieshoek area of the Orange Free State in 1899. He worked at various times as a teacher, a miner, and a full-time political organiser and journalist. In 1926 he joined the CPSA, becoming one of its most loyal African adherents in the years that followed. For a period in the early 1930s he studied at the Lenin School in Moscow. His wife, Josie Mpama, was the only African woman of note in the party at this time.
After organising for the Communist Party of South Africa (CPSA) in Potchefstroom in the late 1920s, Mofutsanyana went to Durban as an organiser in 1931 but was deported back to the Transvaal. For most of the 1930s he was on the party's political bureau, serving as general secretary until 1939 when Moses Kotane assumed the position. In the 1940s he chaired the party's Johannesburg district committee and also served on the central committee and as editor, from 1945, of Inkululeko, the Communist paper. He was one of those charged with fomenting the African mineworkers' strike of 1946. In 1937, 1942, and 1948 he ran as a Communist candidate for election to the Natives' Representative Council but was always defeated. Reserved and slow of manner, he lacked the dynamism necessary for popularity as a mass leader.
Mofutsanyana attended the meetings of the All African Convention (AAC) in 1935 and 1936, each time being elected to the AAC's executive committee. His more long-term concern, however, was with building the ANC into an effective organisation, and in 1937 he joined J. B. Marks, S. S. Tema, and others in reviving the Transvaal ANC. Under A. B. Xuma in the 1940s he served on the African National Congress's (ANC) national executive committee as an advisor on labor matters, and in 1943 he was one of the signatories of Africans' Claims.
In 1944 - 1945 he was on the working committee of the National Anti-Pass Council. A member of Johannesburg's Orlando township advisory board from the late 1930s, he ran in 1945 for president of the Location Advisory Boards Congress but was heavily defeated by the incumbent, R. H. Godlo. In the late 1940s he was active in the Johannesburg squatter's movement, which had originated in the housing crisis of the war years.
He was on the Executive Committee of the Communist Party of South Africa when it was banned and dissolved in 1950, and was one of the foremost among those who worked to build the South African Communist Party underground. He went into exile in Lesotho in 1959. In 1992, he returned to Witzieshoek, where he was born, and, in 1995, he died there.