According to Thucydides, the League's opening campaign was against the city of Eion, at the mouth of the Strymon river. Since Thucydides does not provide a detailed chronology for his history of the league, the year in which this campaign took place is uncertain. The siege seems to have lasted from autumn of one year into the summer of the next, with historians supporting either 477–476 BCE or 476–475 BCE. Eion seems to have been one of the Persian garrisons left in Thrace during and after the second Persian invasion, along with Doriskos. The campaign against Eion should probably be seen as part of a general campaign aimed at removing the Persian presence from Thrace.

The force which attacked Eion was under the command of Cimon. Plutarch says that Cimon first defeated the Persians in battle, whereupon they retreated to the city, and were besieged there. Cimon then expelled all Thracian collaborators from the region in order to starve the Persians into submission. Herodotus indicates that the Persian commander, Boges, was offered terms upon which he might be allowed to evacuate the city and return to Asia. However, not wanting to be thought a coward by Xerxes, he resisted to the last. When the food in Eion ran out, Boges threw his treasure into the Strymon, killed his entire household and then immolated them, and himself, on a giant pyre. The Athenians thus captured the city and enslaved the remaining population.

After the fall of Eion, other coastal cities of the area surrendered to the Delian League, with the notable exception of Doriscus, which was "never taken". The Achaemenids probably recalled the Governor of Doriscus Mascames with his garrison around 465 BCE, and finally abandoned this last Achaemenid stronghold in Europe.