According to the mythology Astypalea was a woman abducted by Poseidon in the form of a winged fish-tailed leopard.
On April 12, 1912, during the Italo-Turkish War, a detachment of the Regia Marina landed on Astypalea, which thus became the first island of the Dodecanese to be occupied by Italy. In a September 1943 naval battle near Astypalea, the Greek destroyer Vasilissa Olga together with the British destroyers HMS Faulknor and Eclipse sank a German convoy, consisting of the transports Pluto (2,000 tons) and Paolo (4,000 tons).
The island is known in Italian as Stampalia and in Ottoman Turkish as Istanbulya.
In 1947, through the Treaty of Paris, it became part of Greece along with the rest of the Dodecanese island group.