Ryanair is to close its base at Valencia, resulting in a loss of 70 flights a week and 750 jobs in the region.
The low cost airline operated flights from Stansted, the East Midlands and Liverpool to the Spanish city.
Most services will be cancelled from November 4, although a limited number of flights will continue to operate from Stansted. All passengers booked on a cancelled flight will receive a refund.
Ryanair said the decision had been taken following the refusal of the local council to “engage in constructive discussions in relation to the promotion of the airport and its routes across Ryanair’s network in Europe.”
A statement said the council had refused to promote the region due a lack of funds, but at the same time granted 12 million euros to support marketing for the local airline, Air Nostrum.
Ryanair deputy chief executive Michael Cawley said: “This is a very black day for the airport of Valencia and the city and region which it serves.
“We have already received numerous enquiries right across Europe and we will be announcing a new base elsewhere next week with these two aircraft.”