The carrier is operating Boeing 777-200 daily flights between New York and Tel Aviv, as well as flights three times per week between Miami and Tel Aviv.
Flights on the routes will carry 15 tonnes of cargo, depending on passenger load factors.
'There is a real market demand, not only for service to our hubs in New York and Miami but also for connections to onward destinations. We're excited to keep the world's goods moving with the addition of these routes and provide more connections for customers,' said managing director of cargo sales Tim Isik.
American Cargo will also launch a Boeing 787-9 service three times per week between Dallas and Fort Worth International Airport (DFW) and Tel Aviv.