In Greek mythology, Serifos is where Danaë and her infant son Perseus washed ashore after her father Acrisius, in response to an oracle that his own grandson would kill him, set them adrift at sea in a wooden chest.

In the late 19th century Serifos experienced a modest economic boom from the exploitation of the island's extensive iron ore deposits.

Worked blocks of island marble built into the walls of the medieval castle crowning Chora, the hilltop main town of Serifos, show that the ancient capital was there as well.

At least four other ancient towers have been located, including the megalithic Psaros Pyrgos (Ψαρός Πύργος) or "Couch of the Cyclops" in the SW corner of the island.

The so-called "Castle of the Old Lady" (Κάστρο της Γριάς) above Ganema and Koutalas preserves scant remains of a collapsed dry-stone construction in a notch below the twin rocky summits.

Rough fragments of white marble and rooftile, and archaic fine-ware potsherds on the SE terraces of the hillside suggest the existence of an ancient sanctuary.

[6] By subsequent writers, Serifos is almost always mentioned with contempt on account of its poverty and insignificance[7] and it was for this reason employed by the Roman emperors as a place of banishment for state criminals.

In the summer of 1916, in response to low pay, excessive working hours, unsafe conditions, and the company's refusal to rehire workers who had been drafted into the Greek army and recently demobilized, the 460 miners formed a union and organized a strike.

Their leader was Constantinos Speras, a Serifos native educated in Egypt, who was an anarcho-syndicalist with long experience of labor struggles on the Greek mainland.