Frankish rule came to an end in 1458 CE with the surrender of the Duchy of Athens to the Ottomans. The Acropolis was transformed into a castle of the Turkish garrison and the Parthenon became a mosque and storage for gun powder. The Erechtheion was used to house the harem.

Irreparable damage was caused to the city during a siege by the Venetians in September 1687 during the the 6th Venetian-Turkish war. Morosini, the general of the Venetian army, turned his cannons towards the Acropolis and one of the shells blew up the gunpowder stored inside. The temple, which until then was structurally almost intact from natural disasters and conquests, suffered extensive damage. Later, the Ottomans built a new small mosque in the opening.

The Acropolis was a scene of conflict during the Greek Revolution, causing additional damage to the monuments. At the same time, the growing interest from Europeans in the culture of Classical Greece resulted in the looting of antiquities. First among these was Thomas Bruce, 7th Earl of Elgin (aka, Lord Elgin). With a vague firman from the Sultan and after bribing Ottoman officialsψ, Elgin managed to extract a large number of the pediment carvings, metopes and parts of the Parthenon frieze, a Caryatid and an Erechtheion column, as well as several parts of the frieze of the temple of Athena Nike. Today, the loot remains in the British Museum.

There are only a few monuments of the Ottoman period that are preserved today. Among these are the Fetiye Mosque inside the Roman Agora, the House of George Finlay and Richard Church in Plaka that also housed a Turkish police station, and the Benizelos House in Plaka that is the last surviving Ottoman-style mansion in Athens. The building of the Madrasah of Athens, the Islamic seminary built in the 17th century, has mostly been destroyed but a single entrance remains in place to the north of the Tower of the Winds. On the branches of the old plane tree in the courtyard, convicts were hanged during the time of King Otto.