Chefs from across the globe will descend on the city’s Euskalduna Centre to discover if New York's Eleven Madison Park will keep the top spot for a second year running.
Chef Daniel Humm’s restaurant knocked Massimo Bottura’s Osteria Francescana off the number one position in 2017.
It will be the third time in the event's 16-year history that the awards have been held outside London, following a move to New York in 2016 and Melbourne in 2017.
“We could not be more thrilled to be returning to Europe to host our event programme in Bilbao, one of the great food destinations of the world,” says William Drew, group editor of The World’s 50 Best Restaurants.
“Come June, Biscay will undoubtedly be the place to be for those passionate about great food and inspirational restaurants.”
Spain has historically had a strong showing in the rankings. The Basque region currently boast four sites in the top 50 list: Asador Etxebarri in Axpe (No.6), Mugaritz near San Sebastian (No.9), Arzak in San Sebastian (No.30) and Azurmendi near Bilbao (No.38).
Nerua – located within the Guggenheim museum in Bilbao – appears on the 51-100 list at No.56, while Martin Berasategui in nearby Lasarte-Oria is ranked No.77.
Ferran Adria’s El Bulli in Roses held the number one spot five times before it closed in 2011, while Girona's El Celler de Can Roca took the title in 2013 and 2015.
This year The World's 50 Best Restaurants has partnered with the Government of Biscay for a five-day celebration, with local events open to the public.
A series of special awards, as well the first recipient of the 50 Best BBVA Scholarship for aspiring chefs, will be announced ahead of the events programme throughout April and May.