Dura-Europos was a Hellenistic, Parthian, and Roman border city built on an escarpment 90 metres above the southwestern bank of the Euphrates river. It is located near the village of Salhiyé, in present-day Syria. Dura-Europos was founded around 300 BC by Seleucus I Nicator, who founded the Seleucid Empire as one of the Diadochi of Alexander the Great. In 113 BC, Parthians conquered the city, and held it, with one brief Roman intermission, until 165 AD. Under Parthian rule, it became an important provincial administrative centre. The Romans decisively captured Dura-Europos in 165 AD and greatly enlarged it as their easternmost stronghold in Mesopotamia, until it was captured by the Sasanian Empire after a siege in 256–257 AD. Its population was deported, and the abandoned city eventually became covered by sand and mud and disappeared from sight.

The Parthian Empire, also known as the Arsacid Empire, was a major Iranian political and cultural power centered in ancient Iran from 247 BC to 224 AD. Its latter name comes from its founder, Arsaces I, who led the Parni tribe in conquering the region of Parthia in Iran's northeast, then a satrapy (province) under Andragoras, who was rebelling against the Seleucid Empire. Mithridates I greatly expanded the empire by seizing Media and Mesopotamia from the Seleucids. At its height, the Parthian Empire stretched from the northern reaches of the Euphrates, in what is now central-eastern Turkey, to present-day Afghanistan and western Pakistan. The empire, located on the Silk Road trade route between the Roman Empire in the Mediterranean Basin and the Han dynasty of China, became a center of trade and commerce.