British Airways will begin operating flights from Leeds Bradford Airport (LBA) to Heathrow from early December, the airline has confirmed.
It will be the first time direct flights have flown from West Yorkshire to the capital since Flybe axed its Gatwick service in March 2011.
Four flights a day will operate between LBA and Heathrow from 9 December.
John Parkin, LBA's chief executive, said the airline's announcement was "outstanding news" for the region.'Welcome return'
"This important new service to Heathrow connects Yorkshire with the world," said Mr Parkin.
"It provides our businesses with the access they need to emerging and established global markets, and enables those markets to easily come to Yorkshire, bringing their investment and inbound tourism direct to our region."
British Airways last operated from Leeds Bradford Airport in 1980.
Andy Lord, British Airways director of operations, said the 160-seater flights from Leeds Bradford Airport to Heathrow were "a welcome return to Yorkshire".
The airport had "a significant catchment area" and would allow customers to connect with both short and long haul flights at Heathrow, said Mr Lord.
Single fares from Leeds Bradford to Heathrow will cost from £42, British Airways confirmed.'Massive boost'
Before axing its flights from Leeds to Gatwick in 2011, Flybe estimated that more than 50,000 passengers had flown from Leeds to the capital in 2010.
Paul Mackie, vice president of Bradford Chamber of Commerce, said since Flybe's departure his members had "lobbied hard" for the re-establishment of flights to London from Leeds Bradford Airport.
The announcement by British Airways was a "massive boost" to the local economy, said Mr Mackie.
"It's not just about us getting down to the south. It's also about those southerners coming up north and doing business in the north too," he said.