The site was initially fortified in the early 13th century by the Byzantine Empire, which employed Venetian architect Giacomo Barozzi to construct a fortress around the promontory.

[2] Upon the fortress' completion, Barozzi was given control of Santorini by fellow Venetian Marco I Sanudo, who had recently coerced the Byzantines into surrendering their claim to the Aegean islands and had named himself Duke of Naxos.

However, the island's trade-based economy suffered, resulting in the ruling families of Santorini severing ties with Venice and signing a non-aggression treaty with the Ottomans.

[5] Without the threat of raids to keep rival settlements in check, Skaros was eclipsed in importance by the towns of Fira (which became the new capital of the island) and Oia.

[2] The 18th century eruptions were notably impactful, as they caused most of Skaros' residents to move to Fira or the nearby village of Imerovigli.