An activist for social justice in the democratic Marxist  and Eco-Socialist tradition, Mazibuko was active in the South African Students Congress and the left-wing Young Christian Students. He was a member of the South African Communist Party, serving as its Spokesperson, including editing the party paper Umsebenzi, and Chief Strategist. He is also a Research Associate at the University of Cape Town’s Centre for Law and Society and a popular educator, researcher and trainer focusing on political economy, cooperatives, food sovereignty, land reform and participatory democracy. Mazibuko has worked in a range of left coalitions and NGOs, including a leading role in the Democratic Left Front and the subsequent United Front (South Africa). He serves as a board member of the Alternative Information and Development Centre. He is the founding Chairperson of the Treatment Action Campaign, an organization that lobbied for a more responsible approach to HIV/AIDS. He has worked as the National Director of the then National Coalition for Gay and Lesbian Equality. Mazibuko was Board Chair of Oxfam South Africa from its founding until November 2020. He was also the Co-Founder of Ntinga Ntaba kaNdoda, a community-based rural movement in the Eastern Cape. He has edited several magazines, such as Amandla Magazine.