Move to "safeguard profitability"
Delta Air Linres is to cut its service between Manchester and New York from January 8, 2010.
The US carrier has been operating the daily service between Manchester International and JFK for three years.
But a spokesperson for the airline said it has taken the decision to stop the service "to safeguard our profitability in the long run".
The spokesperson added: "We are looking at our network like a lot of airlines and matching capacity to meet demand.
"We will be suspending the Manchester-New York service from January 8, because looking at passenger numbers, the demand just isn't there during the winter.
"We will be maintaining the year round Manchester-Atlanta service which will still enable passengers to fly via Atlanta to New York JFK."
Regarding the possibility of reinstating the service next summer, the spokesperson said that Delta would be "monitoring demand for the route."
Manchester Airport spokeswoman said the decision by Delta only covered the winter season and it was "confident" the service would come back in the summer.
She said the two sides were still in talks over the matter.
Delta's is the second airline to withdraw services from Manchester in the past two weeks.
Ryanair announced in August that it was cutting 90% of its services at the airport, affecting 600,000 passengers and 600 jobs, after a row over the airport's fees.
Delta's decision comes after it announced earlier this year it was dropping its Edinburgh-New York route from September 19 with its service between Gatwick and Cincinnati also ceasing at the end of August.
The end of the service will be seen a blow for US-bound passengers located within the Manchester catchment area.
It leaves just Continental Airlines as the only major carrier flying direct from Manchester to New York with a twice daily service.
Pakistan International Airlines also offers a twice-weekly service between the two cities.
BA suspended its flights from Manchester to JFK in October 2008, while bmi also cut its transatlantic services from the airport last year.