After gaining control of Anatolia and expanding the Persian empire's eastern domains, Cyrus II turned his attention to Babylon and took advantage of the unpopularity of the Babylonian king Nabonidus. As elsewhere, Cyrus used askilled propoganda campaign to extol his clemency and tolerance in religious matters. It seems that after the conquests of Media and Lydia, Cyrus had spared the lives of their respective kings, Astyages and Croesus - proof not only of clemency, but also of good diplomacy, for such a policy meant his new subjects would not be alienated.

By the time Nabonidus came to the throne in 555 BC, Babylon was probably not as powerful as it had been under Nebuchadrezzar. Even before the latter's death in 562, there seem to have been anxieties about the possibility of attack, perhaps from the Medes, since toward the end of his reign a defensive wall was constructed north of Babylon. And there is evidence of internal problems, since there were three kings and two rebellions in the seven years between the death of Nebuchadrezzar and the accession of Nabonidus.

Nabonidus was a devotee of the moon god Sin, whose temple at Harran he restored early in his reign. At Ur, he restored the ziggurat of Nana, the ancient Sumerian moon god, but at Babylon he neglected local affairs and religious rituals. These included the cult of Marduk, the city deity, and the New Year festival which renewed the fertility of the land. Only the king could perform this ritual, but for several years his absence at the oasis of Tema in Arabia prevented the performance of this important rite. He had also introduced administrative reforms that effectively gave control of temple finances to the Crown.

Thus there was cause for dissatisfaction among the Babylonians and, in particular, the temple scribes, who gave their support to Cyrus at the fall of Babylon and also compiled Persian propaganda. Their accounts extol Cyrus and claim that Babylon fell without a struggle because Cyrus was welcomed by all. Nevertheless, there seems to have been a fierce struggle when the Persians attacked the Babylonians at Opis early in October 539 BC. It is possible that it was in this battle that Belshazzar, the crown prince known from the Bible, died.

After this victory, Cyrus took Sippar. Then his Gutian troops under Ugbaru, possibly a Babylonian deserter, entered Babylon without a battle on October 12. Nabonidus, who had fled to Babylon from Opis, was captured, and Ugbaru's troops guarded the city peacefully until the arrival of Cyrus at the end of the month. During this time, all the proper religious rituals were observed, and when Cyrus entered the city, he was warmly welcomed.

This conquest gave Cyrus not only Mesopotamia, but the entire Babylonian Empire, which reached to the borders of Egypt. Yet again he showed his clemency and repartriated various exiles, including, it seems from the Book of Ezra in the Bible, Jews who had been deported by Nebuchadrezzar. At some point, he returned to Iran and was killed while campaigning on the northeastern frontier in 530 BC. His body was taken back to Pasargadae, the capital he had built for himself, reputedly at the site of his victory of the Astyages. He was laid to rest in a magnificent stone tomb of great simplicity.