The existence of human life during the Neolithic period (6000 -2600 BC) is proved by archaeological findings in the Ideon Andron cave on Mount Psiloritis, the Gerani cave west of Rethymnon and the Elenon cave in the Amari district.
The greater number of archaeological findings dating back to the Minoan period (2600-1100 BC) can be explained by the fact that human existence and activity became more common both in caves as well as in a variety of other dwelling places, the remains of which cover the entire area of the Prefecture and are evidence of every stage of the Minoan period. Dating back to the Early Minoan period (2600-2000 BC) in the Mylopotamos area are the Sfentoni Cave in Zoniana and Pyrgi, Eletherna, in the Municipality of Rethymno are the sites of Chamelevri, and Apodoulou in the Amari district.
The palatial installations of Monastiraki in the district of Amari, the settlements of Pera Galinous in the Mylopotamos area, and Stavromenou as well as the caves of Melidoni and Patsos in the Municipality of Rethymno date back to the Middle-Minoan period (2000-1600 BC). Finally, the cemetery of Armeni, the settlement of Zominthos in Anoghia and the place of worship in Fantaxospiliara in the village of Prinos date from the Late Minoan period (1600-1100 BC).
During the Geometric and Daedalian period (1100-620 BC) important cities such as Eleftherna and Axos (Oaxos), in the Mylopotamos area, flourished, while at the same time a settlement existed on Mount Vrysina, on the plateau of Onythe. Continuous development of the same areas can also be observed during the period of Antiquity (620-500 BC), when works of great artistic value were produced.
According to the testimony of more recent sources, during Classical (500-330 BC) and Hellenistic (330-67 BC) times, the ancient town of Rithimna must have flourished; it was situated in the same place as the modern town of Rethymno is today. Simultaneously, the other large cities of the prefecture, as for example Eleftherna, Axos, Lappa and Sivrytos continued to exist during the Hellenistic and the Graeco-Roman period (67 BC - 323 AD).
During the First Byzantine period (330-824) when the capital of the Roman Empire was transferred to the Byzantium and Constantinople was founded in 330, Crete was included in the East Roman Empire, constituting a separate district, which was governed by a Byzantine general. Henceforth Christianity expanded on the island, and in the 8th century the Cretan Episcopate was integrated with the Patriarchate of Constantinople. During the early Christian and First Byzantine period a large number of temples were built, archaeologists have discovered many of which.
Starting from the year 824 up until 961, the island was governed by the Arabs, although very little evidence of this fact was found in the area of Rethymno apart from some Arabian coins, which were found in the village of Giannoudi.
During the Second Byzantine period (961-1210) fortification works of the town of Rethymno were started for the first time as we shall see further on. In the year 1211 the long and interesting period of the Venetian occupation began, remains of which can clearly be seen still on all levels in the area of the town of Rethymno.