Born near Vrede in Free State, he was educated at St. Mary's Anglican School, St Chatswold Training College, and then achieved his matriculation in Johannesburg. He then trained as a teacher at Adams College before taking up a teaching post at Orlando Secondary School in Soweto in 1941. He served as President of the Transvaal Teachers Association in 1950. He was first imprisoned in 1960, following the Positive Action Campaign against the Pass laws launched by the PAC. He was imprisoned again in 1963 following the massive police swoop on the PAC underground movement Poqo. He was arrested in connection with Soweto uprisings and charged as accuse no 01 at Bethal Trial. Elected PAC president while he was serving his prison sentence. Mothopeng served three prison sentences for his anti-Apartheid activism on two occasions, and was released by President F. W. de Klerk in 1989. He rejected calls to join political talks aguing that the black people should have all the power. He died a year later.