The ancient city of ´Lato to Camaran´ was lying at the location of the modern city. This city prospered during the archaic, classic times (it was a city-state with its own religion and currency) and during the roman times.
The name of the city comes from the homonymous church, which is one of the most ancient on the island. It concerns about a byzantine church with wall paintings of the iconoclasm period (8th -9th century). The information for Agios Nikolaos starts after the abolition of the Byzantine empire from the latins (1204). The first ruler in Crete after the distribution of the Byzantine land was the Genovese. In 1206 the Genoate pirates built a fortress which they called it Mirabello (=nice view), and this name was given to the bay and the province.
This fortress was later under the occupation of the Venetians and it was burnt by the Turks in 1647. During the times of Venetian domination the harbor of Agios Nikolaos was an important commercial centre. As the rest of Crete, the city fell to the Turkish occupation in 1645.
Near the end of the Turkish domination an significant harbor was built close to Mandraki, which was a small settlement, which was named Agios Nikolaos from the Byzantine church (7th century) which is built at the small peninsula of the harbor.
During the Cretan revolution of the 19th century, Agios Nikolaos was a place where many fights took place and the small harbors of the bay of Mirabello were used as salutary replenishment bases for the rebels.