A new daily service from Heathrow will get under way on 5 November.
Virgin will operate the route using Boeing 787-9 aircraft featuring three cabins – Upper, Premium and Economy.
The winter service will operate until 24 March 2023.
Virgin said the route would complement its year-round daily Johannesburg service.
“We’re incredibly excited to return to the fabulous city of Cape Town with daily services from November," said Virgin Atlantic chief commercial officer Juha Jarvinen.
