Mafela was brought up in Klipton and White City Jabavu, near Johannesburg, and then his family remained until 1990 in the Tshiawelo Township that had been set aside for Venda people under Apartheid. He began acting in movies at age 22, playing the role of an editor in the movie, Real News. He joined the South African film company SA Films, and over the following twenty years he worked as a producer and director as well as a film actor. He also managed the multi-ethnic dance troupes Mzumba, Sangoma, and the Gold Reef Dancers, which performed in feature films, theaters, and hotels and appeared on four continents. In 1974 Mafela co-starred in the first all-black movie made in South Africa, as Peter Pleasure in Udeliwe. He worked with director Peter R. Hunt (famed for the James Bond movie On Her Majesty's Secret Service) in the 1976 film Shout at the Devil.
With the advent of television in South Africa in 1976, Mafela worked almost continuously in that medium. In 1986 he was cast as the unemployed lodger S'dumo in the Zulu language comedy series 'Sgudi 'Snaysi. The success of 'Sgudi 'Snaysi ("Is Good, Is Nice") – which ran to 78 episodes on SABC – led to roles in other series, often produced by Mafela's own production company Penguin Films. It also encouraged Mafela to enter the advertising industry, working as Creative Director of Black Communications at BBDO South Africa and, since 1992, as a director of Sharrer Advertising in Johannesburg.
Mafela conceptualised and starred in early Chicken Licken television commercials, and authored the company's "It's good, good, good, it's good its nice" jingle during the making of a Chicken Licken commercial in 1986.
In 1996, Gallo Records released the album Shebeleza Felas, with the popular hit "Shebeleza (Okongo Mame)". It was a huge success, and "Shebeleza" was a theme song during the Africa Cup of Nations in 1996. Since then, Mafela has recorded and released several other albums of Zulu-language songs.
Sometimes called "the face of South African entertainment", and as "South Africa's Bill Cosby", he starred as recently as 2011 in the thriller Retribution. Nonetheless, the aging Mafela complained in 2012 that it was hard for him to get acting work. He said he's been told that he is "old and cold".