The area of Lassithi has been habited from the Neolithic age attested by evidence found at Trapezas, the village of Magasa near Sitia and tombs on the Kastellos hill in Tzermiado. From 2700 BC new tribes from Asia or Africa occupied the area; then followed the first phase of the Minoan civilisation that continued up to 1700 BC. Settlements were built in: Myrto Ierapetra, Mohlos, Zakos, Paleokastro, Hamezi and the development of ceramics, metalwork and architecture.

After the catastrophe of 1700 BC new settlements were built in Gournia, Psira, Maki Gialo and the creation of naval bases. Later, after 1450 BC catastrophe, Dorians came to the island around 1100 BC and created a new culture and built the cities of Ambelos, Dragmos, Drypos, Lato, Minoa, Olous, Presos and Ierapytna.

During the Hellenic years the cities were destroyed by civil wars and were later captured by the Romans in 66 BC and in 395 AD it became part of the Byzantium Empire. In 824, it was captured by the Moors, but was freed by Nikiforo Foka in 961. During the Venetian rule, from 1204 - 1645, the island was fortified. The Ottomans invaded and captured the island from 1645 - 1897. The residences rebelled against the Turks with a major revolution taking place during the period 1866 - 1869. Union with Greece was affected on 1st December 1913.