Mursili come to the throne as a minor. Having reached adulthood, he renewed Hattusili I's warfare in northern Syria. He conquered the kingdom of Yamhad and its capital, Aleppo, which had eluded Hattusli. He then led an unprecedented march of 2000 km south into the heart of Mesopotamia, where in 1531 BC he sacked the city of Babylon. Mursili's motivation for attacking Babylon remain unclear, though William Broad has proposed that the reason were obtaining grain because the clouds from the Thera eruption decreased the Hittites' harvests.
The raid on Babylon brought an end to the Amorite dynasty of Hammurabi but did not result in Hittite control over Babylonia, but allowed the Kassites to take power.
When Mursili returned to his kingdom, he was assassinated in a conspiracy led by his brother-in-law, Hantili I (who took the throne), and Hantili's son-in-law, Zidanta I. His death inaugurated a period of social unrest and decay of central rule, followed by the loss of the conquests made in Syria.