At Fort Hare he joined the African National Congress (ANC) Youth League and became actively involved in students politics.

In 1957 he organised the Alexandra bus boycotts in which people walked nine miles from the township to the city (Johannesburg) and back every day for three months to protest the increase in fares.

The following year, Nzo went into exile and took up posts in various countries including Egypt, India, Zambia and Tanzania.

[2] After the unbanning of the liberation movements in 1989, Nzo formed part of the ANC delegation that entered into deliberations with the National Party government.

[3] Nzo lost the position of Secretary-General to Cyril Ramaphosa at the ANC July 1991 National Conference held in South Africa for the first time after the unbanning of the liberation movements.

After the first democratic elections in 1994, Nzo was appointed Minister of Foreign Affairs in the government of Nelson Mandela.