Born in Qamata, Cape Province, a brother of George, Ngangomhlaba Matanzima and a nephew of Nelson Mandela, Mathanzima spent part of his childhood at the homestead of Chief Falo Mgudlwa, a repository of Thembu history and lore.

In 1961 he graduated to Chairman of the TTA, survived an assassination attempt in December 1962 by members of the Pan Africanist Congress, and in 1963 was an obvious candidate for Chief Minister of the newly formed Transkeian Legislative Assembly.

According to an article published in Time Magazine at the time, though Transkei declared independence theoretically as a "free state", Mathanzima ruled the territory as a de facto puppet-state dictator, banning local opposition parties and buying at subsidized prices Transkei farmlands offered by the South African government.

[citation needed] In 1979, after the death of AmaMpondo King Botha Sigcau, Mathanzima became State President, with his brother George as Prime Minister.

That party's leader, AbaThembu King Sabata Dalindyebo, was convicted of "violating the dignity" of President Mathanzima, but escaped to Zambia and joined the ANC.

Mandela not only refused but declined to see Mathanzima during his imprisonment on Robben Island, fearing that such a meeting would legitimize the bantustans to the international community.

[7] On 20 February 1986, faced with South African evidence of corruption, Mathanzima was forced to retire as President, although he tried to claim that he wanted to spend more time dealing with family affairs.