Ryanair has confirmed that it will base five aircraft at Barcelona El Prat and launch 20 routes from the airport in September.
The Irish budget carrier will operate seven flight per week to Brussels Charleroi, Dublin, Milan Bergamo, Paris Beauvais and Rome Ciampino.
It will also operate, with fewer frequencies, to Cagliari, Dusseldorf Weeze, Edinburgh, Oslo Rygge and Venice Treviso.
Ryanair will serve the following domestic Spanish routes from its new base: Gran Canaria, Ibiza, Lanzarote, Malaga, Palma, Santander, Santiago, Seville, Tenerife and Valencia.
Absent from the list is the heavily-used Barcelona to Madrid shuttle route.
Ryanair, which already serves the Girona and Reus airports outside Barcelona, says it believes it can "help reverse declining traffic numbers" at the airport, which lost 3 million passengers last year.
Its new base will provide competition for Barcelona-based low-cost carrier Vueling, which had been expecting the move.