Flybe Group (LON:FLYB) will be operating flights from London City Airport from October after signing a five-year deal with the Docklands-based hub.
The new routes to and from Edinburgh, Belfast, Dublin, Inverness and Exeter are on sale now and will start on 27 October.
Flybe will launch five planes for the new operation, which are expected to fly up to half a million passengers a year.
It will be ideal for businessmen and women travelling to the capital given the airport’s proximity to the City and Canary Wharf, with both connected by the Docklands Light Railway (DLR) train service.
The Edinburgh and Dublin routes are expected to be the most popular.
There will also be off-peak flights to selected airports near ski resorts, as well as smaller airports in France and northern Spain.
It follows the launch of eight new routes from Birmingham and another four from Southend with Stobart Air.
Chief executive Saad Hammad said: “Today's announcement is a significant landmark in the re-birth of Flybe. We are delighted to re-enter the London market at London's most convenient airport following a rigorous profitability analysis utilising our strict route assessment model.
“Dedicating five growth aircraft initially to these new routes is a major statement of intent and we look forward to building a successful and growing presence there over the coming years.”
The shares rose 4% to 140p.