The island of Crete (Ottoman Turkish: كریت, romanized: Girit) was declared an Ottoman province (eyalet) in 1646, after the Ottomans managed to conquer the western part of the island as part of the Cretan War, but the Venetians maintained their hold on the capital Candia, until 1669, when Francesco Morosini surrendered the keys of the town. The offshore island fortresses of Souda, Grambousa, and Spinalonga would remain under Venetian rule until 1715, when they were also captured by the Ottomans.

Crete took part in the Greek War of Independence, but the local uprising was suppressed with the aid of Muhammad Ali of Egypt. The island remained under Egyptian control until 1840, when it was restored to full Ottoman authority. After the Cretan Revolt (1866–1869) and especially the Pact of Halepa in 1878, the island received significant autonomy, but Ottoman violations of the autonomy statutes and Cretan aspirations for eventual union with the Kingdom of Greece led to the Cretan Revolt (1897–1898) and the Greco-Turkish War (1897). Despite an Ottoman victory in the war, Crete became an autonomous state in 1898 because of intervention in favour of Greece by European powers and was united with Greece after the Balkan Wars.

During the Cretan War (1645–1669), Venice was pushed out of Crete by the Ottoman Empire. Most of the island fell in the first years of the war, but the capital Candia (Heraklion) held out during a long siege, which lasted from 1648 to 1669, possibly the second-longest siege in history, two years shorter than the First Siege of Ceuta. The last Venetian outposts, the island fortresses of Souda, Gramvousa and Spinalonga, fell in the Ottoman–Venetian War (1714–1718).

There were significant rebellions against Ottoman rule, particularly in Sfakia.

Daskalogiannis was a famous rebel leader who in 1770 led a heroic but foredoomed revolt, which did not get the aid from the Russians, who had instigated it (see Orlov Revolt).

The Greek War of Independence began in 1821, and Cretan participation was extensive. An uprising by Christians met with a fierce response from the Ottoman authorities and the execution of several bishops who were regarded as ringleaders. Between 1821 and 1828, the island was the scene of repeated hostilities. The Muslims were driven into the large fortified towns on the north coast, and it would appear that as many as 60% of them died from plague or famine there. The Cretan Christians also suffered severely by losing around 21% of their population. During the great massacre of Heraklion on 24 June 1821, remembered in the area as "the great ravage" ("ο μεγάλος αρπεντές", "o megalos arpentes"), the Turks also killed the metropolite of Crete, Gerasimos Pardalis, and five more bishops.

As Ottoman Sultan Mahmud II had no army of his own available, he was forced to seek the aid of his rebellious vassal and rival, Muhammad Ali of Egypt, who sent an expedition to the island. In 1825, Muhammad Ali's son, Ibrahim, landed in Crete and began to massacre the majority-Greek community.

Britain decided that Crete should not become part of the new Kingdom of Greece on its independence in 1830, evidently for fear that it would become a centre of piracy, as it had often been in the past, or a Russian naval base in the East Mediterranean. Rather than being included in the new Greek state, Crete was administered by Mustafa Naili Pasha (known as Mustafa Pasha), whose rule attempted to create a synthesis of Muslim landowners and the emergent Christian commercial classes.