BMI Regional is to begin flying between City of Derry Airport and London Stansted with the assistance of a £3.8m grant from the Department of Transport.
The service will begin on Tuesday 2 May, replacing Ryanair's Stansted service.
The airline will operate two return flights each day, except for Saturdays which will have one flight each way.
This is the first-ever UK government backing for a public service obligation (PSO) air route in Northern Ireland.
The Department for Transport provides funding for such routes if the service is "vital for the economic and social development of the region".
It maintains regional airport links through a 'connectivity fund', which can be used to protect important air connections to London which may otherwise be lost.
Secretary of State James Brokenshire said: "The UK government has worked closely with Derry City and Strabane District Council to protect this important route to City of Derry Airport.
"£3.8m of UK government funding will allow 13 return flights to connect Londonderry to London every week.
"The new service will allow business passengers to get to central London and complete a full day's work before returning home."
Jochen Schnadt, chief commercial officer of BMI regional, said the company wanted to invest in the north west.
"It is important for businesses that the region is well connected to the UK capital and BMI Regional is proud to be bringing its quality, premium product to this route," he said.
"Whereas previously, business travellers between Derry and London have had to stay overnight in the city, with our new double daily flights they will now be able to commute there and back in a day, saving both money and time, and hopefully resulting in continued economic growth for the Derry region," he added.
Chief Executive of Derry City and Strabane District Council John Kelpie said they were "delighted" by the deal.
Ryanair axed its service to London last year.