The number of flights will increase from about 300 to 570 a day, the equivalent of opening a medium-sized airport overnight.
The terminal has been dormant since June 15, 2020 to reduce costs during the coronavirus pandemic.
Its shops and cafes have undergone months of refurbishment, updating and cleaning for the reopening.
Gatwick said the expansion in the choice of destinations flown direct from the airport and positive booking data hint at a busy summer ahead.
Chief executive Stewart Wingate said: “A lot of work has gone into preparing our south terminal, and I would like to thank everybody involved as their combined efforts mean that today we are effectively opening a medium-sized airport overnight, which is no small task.
“We’re now ready and excited to welcome passengers back in large numbers, and our restaurants, shops, cafes and bars are also looking forward to serving passengers again before they jet off on holiday, to visit friends and family or take that vital business trip.
“After a difficult two years, we know there is significant pent-up demand for international travel, so I advise passengers to book early to make sure they secure the flights they want this summer”.
He added that the reopening was “great news” for the local community, as well as support and supply businesses that depend on the airport.
British Airways, Wizz Air and Vueling are among the airlines switching from the north to the south terminal between between Sunday and Tuesday.
BA previously announced it will restart its short-haul flights at Gatwick from March 29, with 35 European routes operated by a standalone business.
EasyJet will operate from both terminals as it plans to run its busiest ever flying schedule from the airport with 120 routes.
Gatwick advised passengers to check which terminal their flight is departing from before heading to the airport, to arrive early as terminals may be busy, to make sure their passport is still valid and to check foreign travel advice for their destination countries.