Alexander the Great’s conquests ushered in the Hellenistic era throughout the ancient Mediterranean and Middle East. In this period, the Seleucids, one of most successful of the Successor dynasties, ruled over most of the Middle East at the height of their power. Yet two rising powers in the ancient world, Rome and Parthia, played a crucial role in the decline and eventual fall of the Seleucids. In a prior article, I argued that geopolitical developments around the Eastern Mediterranean in the (...) middle third century BCE were indirectly responsible for the emergence of the Parthian state in Iran. Disastrous military conflicts at home and abroad in the west caused a sudden decline of Seleucid power in the 240s–230s, triggering what political scientists call a power-transition crisis. This article utilizes similar approaches to historical analysis and International Relations theory to contend that, after a period of recovery, a further sudden decline of Seleucid power in the 160s–130s triggered another power-transition crisis that brought an end to Seleucid hegemony over the Middle East permanently. The crisis facilitated the rapid transformation of the Parthian state from a minor kingdom to a major empire, drastically changing the international environment of the ancient world. (shrink)