The county has been inhabited since the Neolithic period. Also, there were many settlements in the Minoan period; archaeological excavations have brought to light many Minoan tombs (e.g. in the Armena area), testimony that there was life in the area in the Minoan period. In antiquity and especially in the Byzantine period, Rethymnon kept pace with the rest of Crete, and presented no significant development. The fiefdoms of the great Byzantine families, the Hortsates, Fokades and Kafatoi were in Rethymnon, where they developed and were active.
During the Venetian occupation, the area prospered and became the spiritual and cultural centre of the island. After Crete was conquered by the Venetians, the island was divided into six sestieri, tenements that were named after districts in Venice. The Castello sestier was made up of the Amarion and Mylopotamos districts, while the San Paolo sestier included the other two districts, Rethymnon and Agios Vassilios. The island's administrative structure changed again after the 14th century, when it was again divided into four administrative districts (territori). Rethymnon was one of them, with the town of Rethymnon as its capital, and this administrative division has been preserved until the present day. During the Cretan revolution in 1866, the epic of Arkadi was written, when its fighters, laymen and clerics, blew themselves up rather than surrender to the Turks. Much later, during the German occupation, the island's inhabitants again exhibited their fighting spirit in all its glory, putting up a fierce resistance against the invaders. As a result, the German troops destroyed many villages in the area and stop ed many innocent civilians. But many heroes also emerged, monuments to whom are preserved and honoured by the Rethymniots.