The airline blamed delays in the planning process over proposals to extend the airport's runway for the decision.
Belfast City Airport Director Katy Best said that because of demand, she was confident that other airlines could be attracted to fill the routes that Ryanair would no longer operate.
Ryanair claims its decision to close its base at Belfast City Airport will result in the loss of 1m passengers.
The airline also said 50 jobs would be lost as would up to 1,000 support roles in and around the airport.
Ryanair CEO Michael O'Leary said the decision was made following confirmation that a public inquiry into a planned runway extension would face further delays.
Ryanair currently carries 800,000 passengers a year from Belfast to five destinations in the UK.
Mr O'Leary said that if permission for the runway extension was granted in the future, Ryanair would return.
The airline has supported the George Best Belfast City Airport's bid to secure a runway extension at its site in the east of the city.
It has been running on a reduced passenger load since its operations were established in October 2007.
There are also restrictions on night-time flying.
A public inquiry was launched into the runway extension after opposition from local residents. It was suspended earlier this summer.
