Flights to both cities will lead in from £17.99 one way, with Lisbon launching daily on October 19 and Kharkiv November 13 flying Tuesdays, Thursdays and Saturdays.
The addition of a ninth Wizz aircraft at Luton has allowed the low cost carrier to increase frequency on three other popular routes.
Flights to Kosovan capital Pristina will increase from three to five a week; Albanian capital Tirana from three to four; and Satu Mare in Romania from two to three.
It also brings Wizz’s total investment in Luton to date to almost $1 billion, supporting 5,300 jobs.
Lisbon and Kharkiv increase Wizz’s UK routes for 2018 to 19, of which 14 are from Luton where the carrier now has 7.17 million seats.
Owain Jones, Wizz Air chief corporate officer, said: “Our ninth new Airbus A321 aircraft will arrive at London Luton at the end of 2018, allowing us to launch two new routes from London Luton to Lisbon and Kharkiv, as well as increase frequencies on some of our most in-demand flights to Pristina, Tirana and Satu Mare.
“Wizz Air’s continued investment in the United Kingdom brings not only more opportunities for our customers to travel to many unique destinations, but also creates more local jobs.”