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Established in Florence, South Carolina, beginning operations on April 1, 1979, with a route connecting Charlotte and Myrtle Beach using Piper Navajo aircraft. The airline expanded its fleet to include de Havilland DHC-6 Twin Otters and acquired Air Carolina in 1980, adding more destinations across the Carolinas, Georgia, and Tennessee.
In 1985, Atlantis joined the Eastern Express system, operating as Eastern Atlantis Express for Eastern Air Lines. The airline upgraded its fleet to British Aerospace Jetstream 31 and Fairchild Swearingen Metroliners, increasing its reach in the southeastern U.S.
Operational and financial challenges led to Atlantis Airlines ceasing operations in 1989.