Loganair will operate eight flights per-day across the working week and a total of 12 at weekends, connecting Cumbria and the Lake District, which receives 45 million visitors per year, to the three destinations.
Both CLDA and London Southend are part of the Stobart Group.
Dublin will also have a daily service each day of the week and Belfast City will be served daily, excluding Saturday.
After a quarter of a century without a fare-paying passenger, Carlisle Lake District airport is to reopen for business this summer in an attempt to swell further the 45 million people a year who head for the national park.
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Tickets go on sale today for a new direct flight route between London and the Lake District, when Carlisle Lake District Airport opens to commercial passenger flights for the first time since 1993. The flights are expected to take about 90 minutes with prices starting at £44.99 one-way.
Stobart Group's head of corporate projects Kate Willard said: "Stobart Group is committed to delivering a brilliant air travel experience across the United Kingdom and Ireland".
The Scottish airline will run flights to the south of England, Northern Ireland and Republic of Ireland from 4 June.
James Duddridge, MP for Rochford and Southend East, said: "I am delighted that Carlisle Lake District Airport plans to launch commercial and business flights on June 4".
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The airport pointed out that anyone flying from it to the U.S. via Dublin will be able to clear US immigration checks in Dublin's Terminal 2 - meaning they will land State side as a "hassle-free domestic passenger".
The terminal building at London Southend Airport.
Now the nearest operational airport to the Lake District is Manchester, around a 90-minute drive to the south. Carlisle Lake District Airport is a 30-minute drive from Penrith, on the edge of the national park.
Carlisle Lake District Airport, owned by the Stobart Group since 2009, typically caters for private aircraft, helicopters and military planes, but tourism bosses are confident the passenger routes will deliver a boost to the region.
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Cumbria Local Enterprise Partnership director Graham Haywood said: "Carlisle Lake District Airport will have a huge impact on Cumbria's visitor economy and is also a key strategic business asset for the county". Our marketing strategy has a key focus on encouraging visitors to stay in the county as a whole.