The SARS-CoV-2 501Y.V2 lineage has been recently been shown to predominate in the Eastern Cape, Western Cape and KwaZulu-Natal provinces of South Africa, all of which experienced major outbreaks of COVID-19. This variant of concern harbours mutations associated with increased transmissibility and neutralizing antibody resistance. In this report, we describe a preliminary analysis of 479 sequences from Gauteng, the country’s economic hub, indicating that the 501Y.V2 lineage first appeared in November and by December accounted for 84% (62/74) of sequences. The Eastern Cape, Western Cape, KwaZulu-Natal and Gauteng data suggests that 501Y.V2 lineage may be predominant throughout South Africa.