Dura-Europos was a Hellenistic, Parthian, and Roman border city built on an escarpment 90 metres (300 feet) 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 (114 AD), 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.

Dura-Europos is of extreme archaeological importance, and was called the "Pompeii of the Desert". As it was abandoned after its conquest in 256–57 AD, nothing was built over it and no later building programs obscured the architectural features of the ancient city. Its location on the edge of empires made for a commingling of cultural traditions, much of which was preserved under the city's ruins. Some remarkable finds have been brought to light, including numerous temples, wall decorations, inscriptions, military equipment, tombs, and even dramatic evidence of the Sasanian siege.

It was looted and mostly destroyed between 2011 and 2014 by the Islamic State during the Syrian Civil War.

Originally a fortress, the city was founded around 300 BC as Dura ("fortress" in Aramaic) at the intersection of an east–west trade route and the trade route along the Euphrates. The city was called Europos by Greeks in honor of the origin of Seleucus Nikator, who founded it and was born in Europos in Macedonia. In ancient times, either designation stood alone; the combination of "Dura-Europos" is modern and was coined by Franz Cumont in 1922.

The city was probably built on the site of a previous town; a clay tablet dating to King Hammurabi of Hana's times, 1900 BC, refers to the place as Da-ma-ra. It is the only cuneiform writing found at Dura; no other evidence has been found. The ancient settlement had probably been deserted for a long time when Dura was founded. The earliest mention of Dura-Europos can be found in the Parthian Stations by the geographer Isidore of Charax (c. 26 BC).

Dura controlled the river crossing on the route between Seleucus's newly founded cities of Antioch and Seleucia on the Tigris. Its rebuilding as a great city after the Hippodamian model, with rectangular blocks defined by cross-streets ranged round a large central agora, took place in the 2nd century BC. The traditional view of Dura-Europos as a great caravan city is modified by the discoveries of local manufactures and traces of close ties with Palmyra. Dura-Europos is now seen as owing its development to its role as a regional capital.

After the siege and destruction of the city its names were forgotten by local people, and the site was known as Salihiyeh, "a name thought to refer to Saladin". In Ottoman times the ruins were known as Qan Qal'esi, "Castle of Blood". Pierre Leriche, excavations director of the site in the early 2000s, opposes the name Dura-Europos, because it "obscures what he sees as the fundamental Greekness of the city" and proposes to use "Europos-Dura" instead.

ἔνθεν Δοῦρα, Νικάνορος πόλις, κτίσμα Μακεδόνων, ὑπὸ δὲ Ἑλλήνων Εὔρωπος καλεῖται.
[Then comes Dura, the city of Nicanor, a foundation of the Macedonians, called Europos by the Greeks.]