Ireland West Airport will cater for the first dedicated transatlantic pilgrimage flight in the facility's history later this year.
The return service, operated by Aer Lingus, will run in August, when a Diocesan pilgrimage from New York will travel to Co Mayo.
When the airport was built in the 1980's, it was envisaged that pilgrimages would play a significant role in generating business.
Today's announcement marks the return of transatlantic flights to Knock for the first time in eight years.
The Chairman of the Airport's board, Joe Kennedy said he hopes it will be a stepping stone in securing regular services for the region in future.
Over 200 pilgrims are expected to travel from the US for the week-long visit.
They will participate in the annual Novena at Knock and visit a number of monastic sites and other places of historic interest in the west of Ireland.
The development comes as a major redevelopment of Knock Shrine continues.
There are plans to update the 38-year-old Basilica and engage in increase promotional activity to attract visitors from Europe and America.
Around 1.6m people visit the shrine every year.