Conflict between the Parthian and Roman empires began in the 1st century BC with disputes over the River Euphrates frontier and the kingdom of Armenia. Seeking fame, the Roman general Crassus launched an attack across the Euphrates in 55 BC. However, the Parthians under King Orodes (reigned 57-37 BC) routed the Romans. Orodes’ son, Phraates IV (reigned 37-3 BC), faced another army under Mark Anthony in 36 BC but forced the Romans to withdraw with a loss of more than 40,000 men. Disputes over the Parthian throne allowed the Romans under Augustus to negotiate the return of their prisoners and peace was established.

During the 2nd century AD Parthia was forced on to the defensive. The Roman emperor Trajan (reigned 98-117) conquered Armenia in 114 and the following year he sacked Ctesiphon, the Parthian capital in southern Mesopotamia. This policy of Roman expansion was reversed under Hadrian (reigned 117-138) and the Parthian king Vologases IV (reigned 148-192) reconquered Armenia and defeated a Roman army. The Romans counterattacked and captured Ctesiphon but were driven back by plague. However, in 198 the Romans sacked the city for the third time in 30 years. Parthian power was weakened and many kings claimed independence, including Ardashir of Persia who founded the Sasanian Empire.