Born in 1913 in Idutywa in the Transkei, Mayekiso was a textile worker and later became president of the African Textile Workers' Union. He was a trade unionist and a leader of the African National Congress in the Cape. He joined the ANC in 1942 and was a leader of the 1949 Port Elizabeth bus boycott and an ANC volunteer during the 1952 Defiance Campaign.

In the mid-1950s he was a member of the Cape ANC executive and also served on the ANC national executive committee. In 1955 he was elected to the executive committee of the South African Congress of Trade Unions. A defendant in the Treason Trial for its full length (1956 to 1961), he was rearrested in 1963 on charges of belonging to the banned ANC. He was convicted and imprisoned for four years. He later died while in detention in 1969.