The low-cost airline will fly three times per week to the airport near the city of Hambantota.
Flights will be launched on June 1 and one-way fares start from Dh179. Wizz Air is the first UAE airline to fly direct between Abu Dhabi and Mattala.
It will also be the only Middle Eastern airline operating the route when it launches in the summer.
“Sri Lanka is an exciting destination that has everything; beautiful beaches, a diverse cultural heritage, historical sites dating back thousands of years and even a Unesco World Heritage Site,” said Michael Berlouis, managing director of Wizz Air Abu Dhabi.
Flights are scheduled to operate on Mondays, Wednesdays, and Fridays, leaving the UAE capital just before 1.30pm. With a flight time of just over five hours, travellers will land in Mattala around 8pm local time.
Why is Mattala the world's emptiest airport?
Having opened in 2013, Mattala Rajapaksa International Airport has previously been called the "world's emptiest airport".
Located about 120 kilometres from Colombo, it was meant to be the nation's second international hub, but has struggled to retain regular international commercial flights since its inauguration.
The country's national carrier, SriLankan Airlines, initially set up a hub operation to the airport, but lack of demand led to the airline pulling out of the route.
Flydubai also previously operated to Mattala with direct flights from Dubai, but dropped the route in 2018.
More options for Sri Lankans visiting home
As well as giving travellers another option for flying to the country, this new route is expected to be a boost for Sri Lankan returning home.
“With Wizz Air's low airfare rates, we anticipate the Sri Lankan employee market in UAE to vastly benefit from travel between the two regions which is expected to be extremely economical,” said Denagama Vitharanage Chanaka, State Minister of Aviation and Export Zones Development.
“I am positive that the route will be a success and wish Wizz Air a successful air operation here in Sri Lanka.”
Mattala Rajapaksa International Airport can accommodate up to one million passengers per year, via a 12,000-square-metre passenger terminal.