The Greeks held out in the Peloponnese until 1460, and the Venetians and Genoese clung to some of the islands, but by the early 16th century all of mainland Greece and most of the Aegean islands were colonized by the Ottoman Empire, excluding several port cities still held by the Venetians (Nafplio, Monemvasia, Parga and Methone the most important of them). The Cyclades islands, in the middle of the Aegean, were officially annexed by the Ottomans in 1579, although they were under vassal status since the 1530s. Cyprus fell in 1571, and the Venetians retained Crete until 1669. The Ionian Islands were never ruled by the Ottomans, with the exception of Kefalonia (from 1479 to 1481 and from 1485 to 1500), and remained under the rule of the Republic of Venice. It was in the Ionian Islands where modern Greek statehood was born, with the creation of the Republic of the Seven Islands in 1800.

Ottoman Greece was a multiethnic society. However, the modern Western notion of multiculturalism, although at first glance appears to correspond to the system of millets, is considered to be incompatible with the Ottoman system. The Greeks with the one hand were given some privileges and freedom; with the other they were exposed to a tyranny deriving from the malpractices of its administrative personnel over which the central government had only remote and incomplete control. When the Ottomans arrived, two Greek migrations occurred. The first migration entailed the Greek intelligentsia migrating to Western Europe and influencing the advent of the Renaissance. The second migration entailed Greeks leaving the plains of the Greek peninsula and resettling in the mountains. The millet system contributed to the ethnic cohesion of Orthodox Greeks by segregating the various peoples within the Ottoman Empire based on religion. The Greeks living in the plains during Ottoman rule were either Christians who dealt with the burdens of foreign rule or crypto-Christians (Greek Muslims who were secret practitioners of the Greek Orthodox faith). Some Greeks became crypto-Christians to avoid heavy taxes and at the same time express their identity by maintaining their ties to the Greek Orthodox Church. However, Greeks who converted to Islam and were not crypto-Christians were deemed "Turks" (Muslims) in the eyes of Orthodox Greeks, even if they did not adopt the Turkish language.

The Ottomans ruled most of Greece until the early 19th century. The first self-governed, since the Middle Ages, Hellenic state was established during the French Revolutionary Wars, in 1800, 21 years before the outbreak of the Greek revolution in mainland Greece. It was the Septinsular Republic with Corfu as capital.