To suppress local opposition, the new Venetian overlords brought in settlers from Venice, giving them land and privileges on Crete. At the same time, forts were built and garrisons established. The Venetian nobility had control of agriculture and imposed heavy taxes on the local people. The Orthodox religion was repressed and a Catholic archbishop headed the Church on the island. A succession of uprisings, mostly led by members of the old Cretan nobility, was harshly quelled. After one rebellion on the Lasithi High Plateau was put down and subsequently habitation there prohibited, even the Venetian settlers objected. A rapprochement began between the two populations and eventually, administrative reforms were introduced. By the early 14th century the island - the ‘Regno di Candia’ - was divided into 6 administrative districts, and then later into four territorii (‘di Candia’, ‘di Rettimo’, ‘della Canea’, ‘di Sitia’) governed by a ‘Rettore’. Overall rule of the island was in the hands of the ‘Duca’, assisted by two advisors (‘Consiglieri’). A captain general and castellans commanded the military.
The capture of Constantinople by the Turks in 1453 signalled a threat to Venetian supremacy in the Mediterranean which was immediately apparent on Crete. The Venetians began a programme of enhanced fortification of the island, financed by higher taxation and carried out using forced labour. Men of literature, artists, theologists and philosophers fled Constantinople and arrived on Crete, establishing themselves around the Church of Agia Ekaterini in Candia (modern Heraklion), a dependency of the prominent Mount Sinai School of learning. Through their direct contact with Renaissance streams of thought that were spreading all over Europe, Crete now became the stage for a blending of Byzantine and Venetian Renaissance culture (Anagénesis). In particular, fresco and icon painting developed to a high art form through the blending of Cretan stylistic components with those of Byzantine icon painting and early Renaissance painting. The style of this Cretan School is represented in the works of the artist Michael Damascenos. His most famous pupil, Doménikos Theotokópoulos, was born in 1541 and spent most of his life in Toledo, Spain, also studying under Titian. His very distinctive paintings embody all the elements of the earlier Cretan School. Today, he is known to the world as El Greco.
However, the clouds were gathering again, and the territorial ambitions of the Turks prompted the two populations of Crete to unite and face an unrelenting enemy. In 1645, Chania was the first city to fall, then Rethymnon a year later. The siege of Candia (Heraklion) began in 1648 and was to last for 21 years. In 1669, Morosini, the last governor of the city, made an honourable withdrawal after a capitulation was negotiated. The forts at Souda and Spinalonga were the last to hold out, until 1715. Now, once again, the island was forced to exchange one occupying force for another – this time, it was the turn of the Ottoman Turks.