The new service will operate three times a week from December 15, 2016 to March 20, 2017.
The airline will use its refurbished A330 fleet.
Tickets will be priced from £699 (new economy) and £949 (new premium) return and will go on sale in December.
Christoph Debus, chief airlines and hotels officer for Thomas Cook, said: “Cape Town really is a ‘wow’ destination for our customers.
"It builds on our Cancun, Cuba and Goa long haul routes from Gatwick which are really popular and more broadly comes on top of new services from Manchester to New York and Miami this year, and to Los Angeles and Boston next year.
