The low cost Hungarian carrier is the first company to resume flights from the UK.
From its base at Luton, flights took off at 07:50 on 1st May to Sofia in Bulgaria. A further two flights were scheduled for the same day.
Passengers could travel on the condition they wore face masks and sat 2 metres apart. There were no in flight meals.
Other airlines such as BA and Easyjet remain grounded due to the Coronavirus pandemic.
Despite UK Government advice not to travel the airline is helping customers to return to family and travel for work.
Wizz Air plans to open more routes including Tenerife and Lisbon in Portugal.