Zamokwakhe’s professional experience started in 2001 as an intern at the Department of Communications. In 2002, together with his classmates at the University of Stellenbosch, they established a small, black-owned ICT-electronics company called Africa SpaceTech Solutions (ASTS) (Pty) Ltd which was incubated at the Institute for Satellite and Software Applications. He was part of the executive directorship of ASTS, a post he held for two years. In 2004, Zamokwakhe joined ILC (Pty) Ltd, now known as Lerumo (Pty) Ltd, as a logistics, information and communications technology consultant. In 2005, he joined an electronics engineering company called Quality Engineering Development. In 2006, Zamokwakhe joined the Department of Science and Technology (DSI) as a Deputy Director: Information and Communication Technology & Services Industries.

Zamokwakhe is responsible for managing budgets and implementation plans with respect to the ICT research, development and innovation programme of the Department.