The budget carrier will base a single Airbus A321 aircraft at the Sussex airport, with flights starting from 22 October.
New destinations include Lanzarote, Athens, Naples and Valletta.
Wizz has operated from Gatwick since 2016, but it is the first time the carrier has based an aircraft at the airport.
It says the move will offer 450,000 seats a year, create more than 40 jobs and indirectly support upwards of 125 roles in the Gatwick catchment.
Fares lead in from £21.99pp one-way and are on sale now.
It follows Wizz’s announcement last week of a new Doncaster Sheffield base, also set to launch in October, offering routes to Alicante, Malaga, Faro, Larnaca, Lublin (Poland), Kosice (Slovakia) and Suceava (Romania).
With the new additions, by late-October, Wizz’s UK network will operate 119 routes to 69 destinations from 11 UK airports.
Owain Jones, Wizz Air UK managing director, said: "We stand ready to continue to support the UK’s recovery with further growth at key airports."
Gatwick chief executive Stewart Wingate added: "This is encouraging news for Gatwick, particularly at a time when the industry has been so negatively impacted by Covid-19.
"Having a new aircraft based at Gatwick underpins the resilience of our business for the long-term and ensures we continue to offer our passengers great choice.
"This is a welcome indication of the positive conversations we are having with airlines – both existing and new - about securing Gatwick’s future."
Wizz will launch four-times-weekly flights to Athens and Naples, operating on Tuesday, Thursdays, Saturdays and Sundays, from 22 October.
A day later, it will launch three-times-weekly flights to Lanzarote and Valletta, operating on Mondays, Wednesdays and Fridays.
