Around 208 Vologases VI succeeded his father Vologases V as king of the Arsacid Empire. He ruled as the uncontested king from 208 to 213, but afterwards fell into a dynastic struggle with his brother Artabanus IV, who by 216 was in control of most of the empire, even being acknowledged as the supreme ruler by the Roman Empire. The Sasanian family had meanwhile quickly risen to prominence in their native Pars, and had now under prince Ardashir I begun to conquer the neighboring regions and more far territories, such as Kirman. At first, Ardashir I's activities did not alarm Artabanus IV, until later, when the Arsacid king finally chose to confront him.

The Battle of Hormozdgan was the climactic battle between the Arsacid and the Sasanian dynasties that took place on April 28, 224. The Sasanian victory broke the power of the Parthian dynasty, effectively ending almost five centuries of Parthian rule in Iran, and marking the official start of the Sasanian era.

Ardashir I assumed the title of shahanshah ("King of Kings") and started the conquest of an area which would be called Iranshahr (Ērānshahr). Vologases VI was driven out of Mesopotamia by Ardashir I's forces soon after 228. The leading Parthian noble-families (known as the Seven Great Houses of Iran) continued to hold power in Iran, now with the Sasanians as their new overlords. The early Sasanian army (spah) was identical to the Parthian one. Indeed, the majority of the Sasanian cavalry composed of the very Parthian nobles that had once served the Arsacids. This demonstrates that the Sasanians built up their empire thanks to the support of other Parthian houses, and has due to this has been called "the empire of the Persians and Parthians".