In the first half of the second century, the Parthian Empire had been divided, but king Vologases IV had reunited it and even increased its influence in Armenia, where he had managed to get his son Vologases V appointed. In the year 180, this younger Vologases succeeded his father as king of Parthia.
All seemed well, but after several years, Vologases V backed the wrong horse in a Roman civil war: his ally Pescennius Niger was defeated by the emperor Septimius Severus (194) and the Romans declared war. In 195, they conquered Nisibis and Edessa, including them in a new Roman province, Mesopotamia. Two years later, Severus captured the twin cities of Seleucia and Ctesiphon, the capitals of the Parthian Empire.
Parthia was seriously weakened. When Vologases V died in 208, he was succeeded by his son Vologases VI, who would be the uncontested ruler until another Roman intervention, in 216, by the emperor Caracalla. Although the Parthians managed to survive this crisis as well, another son of Vologases V, Artabanus IV, had already revolted.
It seems that this revolt had started in 214 (and it is possible that this was the opportunity Caracalla had been looking for). When Caracalla arrived on the scene, Artabanus controled the eastern provinces and Susa, while Vologases VI still held the capital cities, Ctesiphon and Seleucia on the Tigris. In 216, Caracalla ordered the annexation of two buffer states, Edessa and Armenia, to improve the Roman positions before the war was to start. The Armenians refused to come to terms, but Edessa surrendered and offered hospitality to the emperor.
Now, Caracalla asked Artabanus permission to marry his daughter. If this proposal was serious, he later changed his mind, because when Artabanus appeared in the spring of 216, the Romans unexpectedly attacked the visitors. The Parthian managed to escape, but the war had begun, and the Roman army marched to the east, reached Nisibis, crossed the river Tigris, and invaded Adiabene. It is unclear what happened next, but at this point, Caracalla was assassinated and succeeded by Macrinus, who inherited the Parthian War.
In the early summer, king Artabanus and emperor Macrinus met near Nisibis, and the outcome is presented in our sources as a Roman defeat. The sources, however, are generally hostile towards Macrinus, and perhaps the fight was less decisive than is assumed. In any case, an armistice was concluded, and the Romans agreed to pay an indemnity. Later, this was regretted, but in the summer of 217, it was not a bad idea to blame Caracalla for the crisis, search for peace, and concentrate upon other things. After all, the new emperor still had to consolidate his power, and Artabanus was still involved in a civil war with Vologases.
Still, few observers will not recognized what had in fact happened: Rome had paid an indemnity but had gained more control of Armenia and Edessa. Parthian power was seriously weakened, and a few years later, in 224, one of the subject nations in the Parthian Empire, the Persians, revolted. Their leader was a man named Ardašir, the founder of the Sasanian Dynasty. He defeated Artabanus in 224 near Firuzabad, where a relief commemorates his victory, and captured the cities of Vologases VI, Seleucia and Ctesiphon, in the year 226 (or 228?). The Parthian Empire, which had existed for more than four centuries, had come to an end.
The chronology of the Arsacid kings of the Parthian Empire is less well-understood than, for example, the sequence of Seleucid and Ptolemaic kings or the emperors of Rome. This information is based on the researches by G.R.F. Assar, as published in "Iran under the Arsakids, 247 BC – AD 224/227" in: Numismatic Art of Persia (2011).