Flybe is scaling down its Isle of Man operations, closing its base at the island's airport and handing full control to partner Stobart Air.
The use of "more economically viable" aircraft for UK flights mean a "physical base" will no longer be needed, a spokesman said.
Flights to and from Birmingham, Liverpool and Manchester will continue to run as normal.
But flights will be operated and crewed by staff from Stobart Air.
Flybe's contract to transfer NHS patients to and from the UK will continue.
The airline plans to replace two DeHavilland Q400 aircraft with ATR 72066s, which it said were more suited to shorter routes.
Once both aircraft are in use in March, Stobart Air, which operates the services on behalf of Flybe, will take over "full Isle of Man operations".
A "phased" closure of the base will be completed by the start of summer 2020, the spokesman said.
The changes would have "no impact on customers", he added.
Flybe previously confirmed the route between Ronaldsway and Heathrow was to end next month.
The flights were launched in April but were not included in the airline's winter schedule, which starts on 27 October.
A spokesman said the "trial" route was "only introduced as part of the summer 2019 schedule".
Political member for ports Tim Baker MHK said, although the government was "very happy" the service had been introduced for the summer, there had not been the "level of demand that perhaps there might have been for it".