Born in 1916 in Johannesburg Mathole was a miner and an organiser for the African Mineworkers' Union. He was active in the 1946 mineworkers' strike. He later opened a grocery store in Moroka Township, Johannesburg, and in 1949 became a member of the Moroka Advisory Board. He joined the African National Congress in 1947 and participated in the Defiance Campaign of 1952. He was elected secretary of the Transvaal ANC in 1955, he also served on the national executive committee in the mid-1950s and was one of the accused in the Treason Trial, from 1956 to 1961.