Darende had been known by various names including Taranda/Daranda, and Derindere.

The first known administrative unit in Darende was reportedly established by Hittites. One of the Hittites remains within the district is a pair of lion statues residing around Arslantas region, the west of Darende. In chronological order, the governance to date was controlled by Hittites, Mitanni, Assyrians, Achaemenids, Romans, Byzantines, Umayyads, Abbasids, Seljuks, Danishmends, Rum Seljuks, Ilkhanates, Eretnids, Dulkadirids, Mamluks and Ottomans.

Due to the configuration of the natural canyons surrounding the district (e.g. Tohma Canyon), the district has been reported to be one of the hops residing on trade, migration and military routes connecting various neighbouring regions; as an example, Šuppiluliuma I, who expanded Hittites across the Mediterranean and the Mesopotamia against Egyptian Empire, had been using the district to access the south, and Basil I had been carried out his expeditions against Muslims over the district.

During the Roman reign of 200 AD, Darende was one of the Roman settlements which was deduced from the records that the Roman Emperor Trajan had transformed the neighbouring encampment of Melitene into a municipium against the Parthian Empire during the same period. One of the Roman sites within the district is the Ozan Monument which is a single-chamber mausoleum dating back either 200 AD or 50 AD, presumably a popular monument style in Anatolia during the Hellenistic Period.

Early Muslim conquests reached the region during Caliph Omar's reign and the district was conquered by Habib ibn Maslama for a short period of time, and it was reconquered by the same commander during Mu'awiya I's reign around 653-654. Between 7th and 12th centuries, the administration of the district had changed hands rather frequently; however, Darende seems not to be noted until, for the first time, Taranta had been registered as a bishop under the metropolitan bishop of Melitene in the 13th Notitiae Episcopatuum (12th century).