Irish airline Ryanair is to begin operating a new base at Belfast International Airport from March with flights to London's Gatwick Airport.
Five other routes, which have yet to be announced, will follow in October.
Belfast International Airport has described the announcement as "significant and far reaching".
Ryanair said the move represents a multi-million pounds commitment and will support hundreds of jobs in the local community.
Belfast International Airport has been eyeing up Ryanair ever since the airline quit George Best Belfast City Airport in 2010 over delays in a proposal to extend the runway.
But what has paved the way for the new base is Ryanair obtaining landing slots for Belfast flights at Gatwick, currently run by Aer Lingus, another Irish airline.
Aer Lingus is giving them up in March as part of a condition of its takeover by International Airlines Group last year.
The four-times daily Gatwick service will maintain the slots given up by Aer Lingus as part of the IAG takeover of that airline.
Graham Keddie, Belfast International Airport's managing director, said the four flights to Gatwick each day would "have a dramatic effect on our business".
But he criticised the Northern Ireland Executive, saying that bringing Ryanair to the airport had been achieved "against the drag of the regressive air passenger duty (APD)", a tax on short-haul flights.
"Just think what we could do if our Stormont administration bought into our vision for in-bound tourism growth, new routes and thousands of jobs," he added.
Ryanair currently operates a limited timetable from City of Derry Airport.
The airline has confirmed it has axed its summer service from that airport to Alicante.
It said the route "did not meet load factors" but that it would be increasing its flights from City of Derry airport to Faro.
The only route Ryanair unveiled on Thursday was Belfast to Gatwick, but others are understood to be close to finalisation.
Obtaining routes to Germany in particular are seen as high priorities for tourism and the wider economy.
Ryanair's chief commercial officer David O'Brien said the airline would make its decisions on destinations on a commercial basis.
"We are hopeful that we can introduce some new European routes of a business nature and some sunshine routes at much-needed lower fares," he said.
"But it will largely depend on the cost base available and it is fair to say the APD, that tax disadvantage, limits those opportunities."
Belfast International Airport handled 4.4 million passengers in 2015.
Both it and Belfast City Airport have been losing to Dublin Airport, which is breaking passenger records, helped by the Republic of Ireland's abolition of APD.
A move to reduce or abolish APD has previously been ruled out by Stormont because the tax revenue lost to the Treasury, which would amount to tens of millions of pounds, would have to be cut from the block grant provided by Westminster.
In a statement, Enterprise Minister Jonathan Bell made no reference to APD but said he was taking a "keen interest in how we can maximise" the investment by Ryanair and Belfast International Airport.
However, Mr Bell added that he was close to making a final decision on whether to finance a new air route development fund.
Previously, grants of public money have assisted the start-up of services to the likes of New York.