The city of Kydonia continued to flourish during the 1^st Byzantine period, until the Arabic occupation. Christianity started to spread in the island during the 1^st century. The Eparch of Kydonia participated in the 342-343 meeting of Sardiki (Sofia), and his name is recorded in meeting reports and Church documents until the 9^th century. Tombs and tomb inscriptions found in the Church of Aghios Ioannis and in the region where the orphanage is located today indicate the position of the city's cemeteries during this period. 

During this period, Byzantium focused on its interests in the East. As a consequence, Crete and other provinces of the Empire fall into obscurity and in a state of historical lethargy. Later, Crete becomes an independent administrative region under the supervision of a Byzantine General. The administrative and military center of Crete was the city of Gortyna. The population of Crete during the 1^st Byzantine period was of Greek ethnicity and had been converted to Christianity. The island suffered from the attacks of the Arab pirates and from natural disasters and these two factors resulted in the decay of many cities and had serious consequences in the social and economic life.  Crete did not posses a strong and organized defense during this period and the Byzantine navy was not sufficient for the protection of the island.