Now, after Ashurbanipal's death, Babylon, which had been razed less that 70 years earlier and again subdued a littler over 20 years earlier by Ashurbanipal, was ready to pounce. With the ascent of the Chaldean Nabopolassar, who represented now a long drive for vengeance by Babylon and Chaldaea, with the help of the Medes under king Cyaxares - an Iranian tribe gaining power in the east - attacked Assyria. In 612 Nineveh, the capital of Assyria, fell (with the Assyrian king, Sin-shar-ishkun, dying in his palace while under attack) never to be rebuilt again. In 610 Harran, the last Assyrian stronghold fell. Ashur-uballit, the leader of the remaining Assyrian forces failed to retake Harran in 609, and this heralded the fall of Assyria. Assyria was divided between the Chaldaeans and the Medes, the latter taking all of the northern regions, stretching to Ururte and Anatolia while the former taking the southern portions.

This division of spoils put the entire northern region of Mesapotamia and Asia Minor under Iranian influence; Assyria's centralized government allowed for a quick shift in power, while maintaining the integrity of the governability of the region. Cyaxares had also subdued much of the Iranian plateau, putting a vast region under Median control. This, in turn, allowed the Persians, another amalgum of tribes to the south of the Medes in the region called Persa (by the Greeks called Persis), to, under the guidance of Cyrus the Great, take power only 30 years later. However, before this occured, a relative peace in the region was observed in the first half of the 6th century B.C.E.