The outspoken budget airline chief executive launched a blistering attack on the Stormont authorities as he announced that Ryanair would stop using the airport from October 31.
While the 50 Ryanair staff working on the Belfast routes will be offered redeployment opportunities, Mr O'Leary claimed the move would cost 1,000 other jobs that rely on the operator's presence in the city.
His decision comes after a planning application lodged two years ago to extend the runway by around 600 metres (1,968ft), thus opening it up to further afield destinations, was referred to public inquiry by the Stormont government.
"If Belfast doesn't want (it) and the authorities up here don't recognise that Ryanair wants to invest in Belfast, wants to invest in Northern Ireland tourism, but we're not going to beat our head against the bloody wall for more than three years to do it, then to hell with you," said Mr O'Leary.
In a typical colourful press conference in Belfast, the straight-talking entrepreneur said he would be prepared to come back to the airport if the runway was approved.
"I'm now saying we're going to go, we're taking the plane, you'll lose the passengers, you'll lose the jobs, but we'll come back if somebody at some point in time up here makes a f****** decision and delivers us a very small, very modest runway extension to allow us to do nothing other than fly safely from Belfast City to continental Europe," he said.
In the interim, Ryanair flights between Belfast and London Stansted, Liverpool, East Midlands, Bristol and Glasgow Prestwick airports will be withdrawn at the end of October. Passengers who have already booked can apply for a refund.
The airline first set up at the airport in late 2007, operating a number of domestic flights with reduced passenger restrictions while preparing to launch a series of European routes confident that the extension would be granted.
But the proposal was met with fierce opposition by some local residents, who claimed noise levels would soar if planes with heavier payloads were allowed to use the airport.
In the face of competing claims, in March this year Stormont Environment minister Edwin Poots referred the matter to the Planning Appeals Commission to conduct a public inquiry. But while the independent probe was due to be undertaken by the end of this year it has been hit by a number of delays and has not yet started.
Mr O'Leary said he regarded the Belfast operation as a success and that a million passengers were now using it annually.
He stressed he was not opposed to the principle of a public inquiry, just the delay in getting a decision.
"We fully recognise that Northern Ireland is a democracy," he said.
"We also recognise the right of people to go to public inquiry but I resent the fact that it takes three years to get there, and even when it goes to public inquiry then the public inquiry is going to be further delayed."
The Ryanair plane based in Belfast will now be moved to Spain or Italy.
George Best Belfast City Airport Business Development director Katy Best said she was disappointed at Ryanair's decision.
"However, passenger figures had proved that there was significant demand for the routes operated by Ryanair and I am confident that we can attract other airlines to fill the void," she said.
Minister Poots also expressed disappointment with the news.
"There has been an economic downturn and as a consequence airline companies are cutting their cloth," he said.
"Northern Ireland unfortunately has failed to meet requirements for Ryanair."
While the minister suggested the airline could have operated European flights from Belfast International Airport, Mr O'Leary ruled out any move to the facility at Aldergrove, declaring he was not interested.
Liz Fawcett, spokeswoman for Belfast City Airport Watch, a residents' group opposed to the runway extension, welcomed the move but expressed concern another operator would take Ryanair's place.
"Ryanair thought it could come in and dictate airport policy in Northern Ireland, and we're really glad they've discovered they can't," she said.
"But, while we welcome the move, the City Airport will now be busy enticing airlines such as easyJet to bring more routes to the airport, so any respite from noise for residents is likely to be short-lived."
But retailers said the pull out was not good news for the region.
Northern Ireland Independent Retail Trade Association Chief Executive Glyn Roberts said: "This is very bad news for both Belfast City Airport and the local economy as a whole.
"Many visitors from the five Ryanair UK routes shopped in Belfast City Centre and other towns and cities throughout Northern Ireland.
"Struggling retailers will be disappointed that the loss of these routes will mean fewer customers from other parts of the UK.
"Air routes such as these are absolutely vital for Northern Ireland developing its tourist potential and as a location for major UK conferences. We simply cannot afford to lose them."
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