The airline's direct flights between Dublin and Washington and Dublin and San Francisco will stop from 25 October.
Flights between Shannon and Chicago will also be suspended over the winter period, from 1 September.
The airline also said the whether the routes would begin again was "subject to review".
Pilots and cabin crew have been offered unpaid leave in order to deal with the surplus of staff that will arise from the cutbacks.
Aer Lingus said the four times a week Shannon to New York JFK remained under review.
Aer Lingus Chairman Colm Barrington said he hoped the move would "safeguard the long-term viability" of the company.
"These changes to our schedule are absolutely necessary given the unprecedented operating environment and legacy practices in our long haul business which are no longer sustainable," he said.
From October an A320 aircraft will be based at Shannon. Aer Lingus said it hoped to be able to provide a three times a day flights to Heathrow, dependent on availability of slots.
The airline ended the route in January 2008, a move which caused anger in the Shannon area.
In May it was announced that Aer Lingus was making cuts to its Belfast operations.
It is removing one of three planes operating out of Belfast International Airport until the beginning of March 2010.
Flights to Paris, Rome, Milan, Faro and Barcelona flights will be suspended for the winter.
