Originally a fortress, it was founded in 303 BC with the name Dura by Seleucus I Nicator on the intersection of an east-west trade route and the trade route along the Euphrates.
Dura controlled the river crossing on the route between his newly founded cities of Antioch and Seleucia on the Tigris.
Its rebuilding as a great city built after the Hippodamian model, with rectangular blocks defined by cross-streets ranged round a large central agora, was formally laid out in the 2nd century BC.
 The traditional view of Dura-Europos as a great caravan city is becoming nuanced by the discoveries of locally made manufactures and traces of close ties with Palmyra (James).
Instead, Dura Europos owed its development to its role as a regional capital.

In 113 BC, the Iranian Parthians conquered Dura-Europos, and held it, with one brief intermission, until 165 AD, when it was taken by the Romans.
The Parthian period was a phase of expansion at Dura Europos—an expansion favored by abandonment of the town's military function.
All the space enclosed by the walls gradually became occupied, and the installation of new inhabitants with Semitic and Iranian names alongside descendants of the original Macedonian colonists contributed to an increase in the population, which was a multicultural one, as inscriptions in Greek, Latin, Aramaic, Hebrew, Syriac, Hatrian, Palmyrene, Middle Persian, Parthian, and Safaitic testify.
In the 1st century BC, it served as a frontier fortress of the Parthian Empire.

The entirely original architecture of Dura Europos was perfected during the Parthian period.
This period was characterized by a progressive evolution of Greek concepts toward new formulas in which regional traditions, particularly  Babylonian ones, played an increasing role.
These innovations affected both religious and domestic buildings.
Although Iranian influence is difficult to find in the architecture of Dura Europos, in figurative art the influence of Parthian art is evident.

In 114 AD, the Emperor Trajan occupied the city for a couple of years: the Third Cyrenaica legion erected a "Triumphal Arch" to the west of the Gate of Palmyra.
Upon the death of Trajan in 117, Rome relinquished Mesopotamia to the Parthians.
Dura was retaken by the Roman army of Lucius Verus during the Roman–Parthian War of 161–166.

The townspeople however retained considerable freedom as a regional headquarters for the section of the river between the Khabur and modern Abu Kemal.
As historian Ross Burns states, in exchange the city's military role was abandoned.
Its population, originally based on the Greek settler element, were increasingly outnumbered by people of Semitic stock and by the first century BC, the city was predominantly eastern in character.
The Romans called the city by the name Dura Europus, because the local aristocracy was composed of Macedonian descendants (identifying that the city was ruled by "Europeans" from Macedonia).

Romans used the city as a starting point for the conquest of the territories of Osroene and as outpost for expeditions against the Parthian empire and their Tigris capital in 198 AD.
The city later was a border post of the Roman "Kingdom of Palmyra".

In A.D. 194, Emperor Septimius Severus divided the province of Syria to limit the power of its previously rebellious governors.
As a result, Dura became part of the new province of Syria Coele.
In its later years, it also attained the status of a Roman colonia, which, by the third century, was what James (Henry Breasted) calls an “honorary title for an important town.”
He suggests that the “Roman authorities wanted to present Dura as an important city of the Roman province.”

— Dura-Europos: Crossroad of Cultures by Carly Silver
The military importance of the site was confirmed after 209 AD: the northern part of the site was occupied by a Roman camp, isolated by a brick wall; soldiers housed between the civilians, among others in the so-called "House of Scribes".
Romans built the palace of the commander of the military region, on the edge of a cliff.
The city then has several sanctuarie
Originally a fortress, it was founded in 303 BC with the name Dura by Seleucus I Nicator on the intersection of an east-west trade route and the trade route along the Euphrates. Dura controlled the river crossing on the route between his newly founded cities of Antioch and Seleucia on the Tigris. Its rebuilding as a great city built after the Hippodamian model, with rectangular blocks defined by cross-streets ranged round a large central agora, was formally laid out in the 2nd century BC.  The traditional view of Dura-Europos as a great caravan city is becoming nuanced by the discoveries of locally made manufactures and traces of close ties with Palmyra (James). Instead, Dura Europos owed its development to its role as a regional capital.
In 113 BC, the Iranian Parthians conquered Dura-Europos, and held it, with one brief intermission, until 165 AD, when it was taken by the Romans. The Parthian period was a phase of expansion at Dura Europos—an expansion favored by abandonment of the town's military function. All the space enclosed by the walls gradually became occupied, and the installation of new inhabitants with Semitic and Iranian names alongside descendants of the original Macedonian colonists contributed to an increase in the population, which was a multicultural one, as inscriptions in Greek, Latin, Aramaic, Hebrew, Syriac, Hatrian, Palmyrene, Middle Persian, Parthian, and Safaitic testify. In the 1st century BC, it served as a frontier fortress of the Parthian Empire.
The entirely original architecture of Dura Europos was perfected during the Parthian period. This period was characterized by a progressive evolution of Greek concepts toward new formulas in which regional traditions, particularly  Babylonian ones, played an increasing role. These innovations affected both religious and domestic buildings. Although Iranian influence is difficult to find in the architecture of Dura Europos, in figurative art the influence of Parthian art is evident.
In 114 AD, the Emperor Trajan occupied the city for a couple of years: the Third Cyrenaica legion erected a "Triumphal Arch" to the west of the Gate of Palmyra. Upon the death of Trajan in 117, Rome relinquished Mesopotamia to the Parthians. Dura was retaken by the Roman army of Lucius Verus during the Roman–Parthian War of 161–166.
The townspeople however retained considerable freedom as a regional headquarters for the section of the river between the Khabur and modern Abu Kemal. As historian Ross Burns states, in exchange the city's military role was abandoned. Its population, originally based on the Greek settler element, were increasingly outnumbered by people of Semitic stock and by the first century BC, the city was predominantly eastern in character. The Romans called the city by the name Dura Europus, because the local aristocracy was composed of Macedonian descendants (identifying that the city was ruled by "Europeans" from Macedonia).
Romans used the city as a starting point for the conquest of the territories of Osroene and as outpost for expeditions against the Parthian empire and their Tigris capital in 198 AD. The city later was a border post of the Roman "Kingdom of Palmyra".
In A.D. 194, Emperor Septimius Severus divided the province of Syria to limit the power of its previously rebellious governors. As a result, Dura became part of the new province of Syria Coele. In its later years, it also attained the status of a Roman colonia, which, by the third century, was what James (Henry Breasted) calls an “honorary title for an important town.” He suggests that the “Roman authorities wanted to present Dura as an important city of the Roman province.”
— Dura-Europos: Crossroad of Cultures by Carly Silver
The military importance of the site was confirmed after 209 AD: the northern part of the site was occupied by a Roman camp, isolated by a brick wall; soldiers housed between the civilians, among others in the so-called "House of Scribes". Romans built the palace of the commander of the military region, on the edge of a cliff. The city then has several sanctuarie
Dura-Europos