Virgin Atlantic has blamed "Increasing costs and a challenging economic environment" for its decision to dump its Sydney to Hong Kong service as from May 5.
The last flight departing Hong Kong to Sydney will be May 4.
The airline said the route was no longer considered profitable.
Virgin Atlantic will continue to operate services between London Heathrow and Hong Kong.
Staff based in Sydney and Hong Kong will be affected.
Craig Kreeger, Virgin Atlantic CEO, said: "These are still difficult times for the airline industry and we need to deploy our aircraft to routes with the right level of demand to be financially viable."
