Although he was a younger son, Esarhaddon had already been proclaimed successor to the throne by his father, Sennacherib, who had appointed him governor of Babylon some time after Sennacherib sacked that city in 689. Sennacherib was murdered (681) by one or more of Esarhaddon's brothers, apparently in an attempt to seize the throne. Marching quickly from the west, Esarhaddon encountered the rebel forces in Hanigalbat (western Assyria), where most of them deserted to him, and their leaders fled. Esarhaddon continued on to Nineveh, where he claimed the throne without opposition.

In southern Babylonia, meanwhile, the leader of a Chaldean tribe took advantage of the revolt and attacked the Assyrian governor at Ur. When Esarhaddon sent troops against the chieftain, he fled northeastward, expecting to find asylum in Elam. Instead the new Elamite king summarily executed him. The rebel's brother, however, escaped to Assyria and submitted to Esarhaddon, who appointed him a local ruler in his dead brother's place. This rare instance of Assyrian mercy bore rich dividends, for he remained loyal throughout Esarhaddon's reign.

The cities of northern Babylonia, which had suffered severely under Sennacherib, were shown particular favour under Esarhaddon. He restored land to displaced citizens who could make good their claims, and in 678 he took military action against a Chaldean tribe that had encroached on the lands of Borsippa and Babylon.

Farther north the pressure of Cimmerians (Cimmerian) and Scythians (Scythian) was being increasingly felt. Esarhaddon is said to have made a marriage alliance with the Scythians to strengthen his position there. The pressure of the Cimmerians continued, however, and Esarhaddon finally lost control of much of the northwestern provinces of Cilicia and Tabal.

When Egypt (Egypt, ancient) inspired a revolt of the Phoenician city of Tyre, Esarhaddon attacked Egypt (675); he had little success until 671, when he seized Memphis and defeated the Egyptian king Taharqa, who fled south, leaving the entire country to Esarhaddon. For the first time a Mesopotamian ruler included “king of Egypt” among his royal titles. After the withdrawal of the Assyrian army, Taharqa emerged and attracted a considerable following. Esarhaddon was marching to put down the rebellion in 669 when he died. In 672 Esarhaddon had proclaimed detailed instructions for the succession of two of his sons to the thrones of Assyria and Babylonia, and at his death the successions were carried out smoothly.