The Egyptian satrapy of the Persian Empire was particularly prone to revolts, one of which had occurred as recently as 486 BCE. In 461 or 460 BCE, a new rebellion began under the command of Inaros, a Libyan king living on the border of Egypt. This rebellion quickly swept the country, which was soon largely in the hands of Inaros. Inaros now appealed to the Delian League for assistance in their fight against the Persians.

There was a League fleet of 200 ships under Admiral Charitimides already campaigning in Cyprus at this time, which the Athenians then diverted Egypt to support the revolt. Indeed, it is possible that the fleet had been dispatched to Cyprus in the first place because, with Persian attention focused on the Egyptian revolt, it seemed a favourable time to campaign in Cyprus. This would go some way towards explaining the apparently reckless decision of the Athenians to fight wars on two fronts. Thucydides seems to imply that the whole fleet was diverted to Egypt, although it has also been suggested that such a large fleet was unnecessary, and some portion of it remained of the coast of Asia Minor during this period. Ctesias suggests that the Athenians sent 40 ships, whereas Diodorus says 200, in apparent agreement with Thucydides. Fine suggests a number of reasons that the Athenians may have been willing to engage themselves in Egypt, despite the ongoing war elsewhere; the opportunity to weaken Persia, the desire for a naval base in Egypt, the access to the Nile's huge grain supply, and from the viewpoint of the Ionian allies, the chance to restore profitable trading links with Egypt.

At any rate, the Athenians arrived in Egypt, and sailed up the Nile to join up with Inaros's forces. Charitimides led his fleet against the Achaemenids in the Nile river, and defeated a fleet consisting of 50 Phoenician ships. It was the last great naval encounter between the Greeks and the Achaemenids. Of the 50 Phoenician ships, he managed to destroy 30 ships, and capture the remaining 20 that faced him in that battle.