The three-times-daily route will begin on June 29th and comes after BMI revealed in March that it would stop its flights to Heathrow from the Yorkshire airport.
Mike Rutter, Flybe’s chief commercial officer, said the flights to the capital "are of great strategic importance" to Yorkshire and the wider northern region.
"The new service demonstrates Flybe’s commitment to the region, continuing to help the local economy through the development of affordable and convenient business and leisure travel options," he commented.
The new business-friendly schedule looks set to create 130 jobs in the Leeds Bradford region, while 20 new positions will be created by the airline at Gatwick.
A Bombardier Q400 will operate the route, with tickets having gone on sale from £24.99.
Flybe recently launched a recruitment drive for local cabin crew in Jersey after its frequency of flights to the Channel Islands increased by 33 percent during summer 2008.