Seven new routes to holiday destinations in continental Europe are to operate from George Best Belfast City Airport.
Bmibaby will run services to Malaga, Alicante, Palma, Faro, Ibiza, Amsterdam and Geneva.
The expansion is coming at the expense of Cardiff airport, with bmibaby stopping operations out of the city this autumn.
The budget airline said it will run its engines on a different thrust setting to enable them to take off from the east Belfast facility.
Other operators have previously insisted they could not fly to Europe from the City Airport until a much delayed application to extend the runway is given the go-ahead. The controversial planning application is due to go before a public inquiry.
Ryanair pulled its operations out of Belfast City last year in frustration at the delays to the runway extension.
Chief executive of the airport Brian Ambrose said: "This is the most significant announcement in Belfast City Airport's recent history and is a welcome reward to all the staff who work tirelessly to make this airport world class."
Julian Carr, managing director of bmibaby, said the airline was committed to Belfast City: "Bmibaby will be the only low-cost airline to operate the new routes directly from Belfast City Airport and this will make getting away for a sunshine, ski or city break more accessible from Northern Ireland."
But Belfast City Airport Watch, one of the most vocal groups opposed to the runway, expressed anger at bmibaby's announcement and claimed residents are annoyed that the facility is being allowed to turn into an international airport.
"It's completely inappropriate for an airport on the doorstep of major residential areas to be permitted to become an international airport when we already have an international airport on a virtual greenfield site just up the road," a spokeswoman said.