Flybe, the airline which has received government help to avert collapse, is planning to scrap its Newquay-Heathrow service in March.
It will replace it with flights from Newquay to London’s Gatwick airport.
It comes just days after ministers said the airline should receive support because of its regional connectivity.
The change is expected to anger businesses in the South West, who value the range of international destinations Heathrow provides.
“Heathrow puts you on the map when it comes to attracting inward investment,” said one regional development official.
Cornwall’s links to London are considered important enough to make the route one of the few in the UK to be operated under a “public service obligation” contract.
This means the government offers a subsidy for the route and invites tenders to operate it.
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The BBC understands that Flybe had been talking to Newquay airport about measures that might mitigate the effects of the change to Gatwick.
Senior industry sources confirmed said the decision to move had now been made and the airline’s website has for some time not been selling Newquay-Heathrow flights past the end of March.
The route will, however, still qualify for public subsidy.
Earlier this week, the government said it would conduct a review of regional connectivity as part of its “levelling up” drive to spread economic growth across the regions.
The announcement was made at the same time as ministers approved help for Flybe, which is thought to centre on giving the airline time to pay about £100m of outstanding air passenger duty.
Following the rescue deal, the Department for Transport said: “In light of these discussions Flybe have confirmed they will continue to operate as normal, preserving flights to airports such as Southampton, Belfast and Birmingham.”
Flybe said it was working closely with its “partners across the network” to finalise its full summer programme. “Our future plans are business confidential and not yet ready for release,” it said.
Separately, the BBC has learned that Flybe will, also from the end of March, be free to divert many of the Heathrow runways slots it uses for domestic flights to other short-haul services.
Flybe was awarded the slots in 2017 as part of “remedy” imposed by competition regulators on British Airways after it bought BMI British Midland.
BA had to surrender the slots - which are highly prized, with pairs selling for £20m or more - as long as the new owner operated them on certain domestic routes.
Flybe is, however, free to change to other short-haul routes from the end of March.
Industry sources said it could use those slots for European flights currently operated by its partner airlines - leaving one of its shareholders, Virgin Atlantic, or its partner Delta Air Lines of America, the chance to start new long-haul services from Heathrow.