Virgin Atlantic is to increase its number of flights from Manchester by up to 20% from 2019 when it will operate up to six departures a day.
It will launch a new service to Los Angeles on May 26, 2019 and increase frequency to both Boston and Las Vegas.
In total, it will offer more than 14,000 seats a week from Manchester to the US and the Caribbean.
Several routes will be operated by a Boeing 747, the largest aircraft in Virgin's fleet.
Due to Virgin's partnership with Delta Air Lines, passengers will be able to connect on to flights to more than 200 US destinations.
Its partnership with Flybe means customers based in other UK regions will be able to connect at Manchester with Virgin's long-haul flights.
Frequency to Las Vegas, one of Manchester's top 10 destinations last year, will double from the end of March 2019 while the frequency of Virgin's Boston service will increase to three flights a week from May 25.
Chief commercial officer Shai Weiss said: "We've always said that Manchester is an important base for Virgin Atlantic and this latest expansion really cements that."
Manchester Airport aviation director Julian Carr said: "It's pleasing to see Virgin Atlantic continuing to grow from Manchester Airport and we are delighted to see the carrier launch a service to Los Angeles.
"The airline's commitment and growth clearly demonstrates the role we play at connecting the north to key global destinations and~the demand to fly direct from Manchester."
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