He was appointed successor to the throne in 37 BC, after the death of his brother Pacorus I. He soon murdered his father and all his thirty brothers.
Phraates was attacked in 36 BC by the Roman general Mark Antony, who marched through Armenia into Media Atropatene, and was defeated and lost the greater part of his army. Antony, believing himself betrayed by Artavasdes, king of Armenia, invaded his kingdom in 34 BC, took him prisoner, and concluded a treaty with another Artavasdes, king of Atropatene.
But when the war with Octavian broke out, Antony could not maintain his conquests; Phraates recovered Atropatene and drove Artaxes, the son of Artavasdes, back into Armenia. But by his many cruelties Phraates had roused the indignation of his subjects, who raised Tiridates II to the throne in 32 BC. Phraates was restored by the Scythians, and Tiridates fled into Syria. The Romans hoped that Augustus would avenge the defeat of the Roman general Marcus Licinius Crassus on the Parthians, but he contented himself with a treaty, by which Phraates gave back the prisoners and the conquered eagles; the kingdom of Armenia also was recognized as a Roman dependency. Soon afterwards Phraates, whose greatest enemies were his own family, sent five of his sons as hostages to Augustus, thus acknowledging his dependence on Rome (the hostages included Tiridates III, whom the Romans later tried to install as a vassal king in AD 35). This plan he adopted on the advice of an Italian concubine whom he made his legitimate wife under the name of "the goddess Musa"; her son Phraates V, commonly called Phraataces (a diminutive form), he appointed successor. About 2 BC he was murdered by Musa and her son.