The flights had been grounded since Covid travel restrictions were introduced in spring last year and the airline had not announced their restoration.
It confirmed today: "Due to ongoing delivery delays with several Boeing 787 aircraft, we’ve made the difficult decision to discontinue service between our Philadelphia hub and Edinburgh and Shannon.
"As a result, American will not resume service to Edinburgh or Shannon in 2022.
"We thank team members who served our customers in Edinburgh and Shannon and are working closely with them during this transition.”
It is understood Edinburgh airport officials had been hopeful flights would be resumed.
The setback comes a day after Virgin Atlantic launched twice-weekly flights from Edinburgh to Barbados.
United Airlines announced last week it would resume year-round flights from Edinburgh to New York in March, and summer flights to Chicago and Washington DC in May.
American Airlines chief revenue officer Vasu Raja wrote in an internal memo published by the airline: “Without these wide-bodies, we simply won’t be able to fly as much internationally as we had planned next summer, or as we did in summer 2019.
"We’ll continue to evaluate these routes as more aircraft become available and would like to be able to serve them again in the future.”
A spokesman for Edinburgh Airport said: “We’re delighted that Edinburgh still features in in American Airline’s future plans.
"We look forward to welcoming them back to Scotland and continuing the great relationship we had with them prior to the pandemic.”