For a time, Seleucus I and his successors commanded the largest empire in the world as it stretched from the high plains and deserts of what is now Afghanistan in the east to parts of the Levant and Asia Minor in the west. The empire's early kings were strong and shrewd and committed to the ideas of Hellenism as much as holding power and expanding the realm of their empire, but later rulers did not prove as capable. In time, the Seleucid royal house often descended into orgies of violence which were driven by ambitious men and women.

One general tied to the Seleucids was Artaxias, who founded the Artaxiad dynasty and managed to unite various Armenian regions under his rule and establish a strong central government, which enabled him to wage successful military campaigns against neighbouring powers. Artaxias I the Pious also built the capital city of Artaxata, which became a cultural and economic centre for the Armenian people. The succeeding kings of the Artaxiad dynasty continued to expand the territory of Greater Armenia, which at its height, stretched from the Black Sea to the Caspian Sea and from the Caucasus Mountains to the Mediterranean Sea.

During the reign of the Artaxiad dynasty, Armenia became a hub of trade and commerce, connecting the Silk Road and the Mediterranean world. The Armenian kings encouraged the development of agriculture, commerce, and arts, and the kingdom became renowned for its skilled artisans, writers, and philosophers. Of course, given its central location, the dynasty also faced numerous challenges, including repeated invasions by the Roman and Parthian empires, internal conflicts, and economic hardships. The dynasty's resilience and adaptability enabled it to survive for nearly two centuries, leaving behind a rich cultural and political legacy that has endured in the region, even as its historical memory was overshadowed by its more powerful neighbors.

After the collapse of the Artaxiad dynasty (at the onset of the 1st century BCE), Rome and the kingdom of Parthia engaged in a competition for political influence in the vast territory of Greater Armenia. The Parthian Arshakunis endeavored to expel Rome from the region, aiming to establish the dominance of their own lineage. The political strategy devised by Parthian King Artabanus III, however, remained unrealized, as his sons Vorodes and Arshak I, who held the throne in Great Armenia, were deposed due to the intervention of the Roman Emperor Tiberius. By inciting the Alban, Georgian, and other neighboring tribes against the Armenians, Tiberius facilitated the ascendancy of Mithridates, the brother of Iberian King Pharasmanes, to the throne of Greater Armenian in the year 36.

This set the pattern by which the Roman Empire sought to preserve its influence in Greater Armenia by employing foreign kings as proxies. In contrast, the Armenian people and their rulers strived to emancipate themselves from Roman hegemony and the dominance of their allies, aspiring to reinstate the sovereignty of the Greater Armenian Kingdom while reestablishing a mutually beneficial military-political alliance with the neighboring Parthian Kingdom.