In the 5th century BC Atalanti was annexed in the Macedonian kingdom and by that time it followed the Greek history.

Refounded in 1760 by Christian settlers from adjoining areas, they chose it as their new home due to its proximity to the Axios River, near the ruins of ancient town Atalanti.

People of Axioupolis Municipality participated in the Macedonian Struggle, and the main leaders of Greek efforts are mentioned below.

Macedonian fighters (Makedonomachi):[5] The "La Macédoine et sa Population Chrétienne" survey by Dimitar Mishev (D. Brankov) from 1905 shows that the local Christian inhabitants were divided between Bulgarian Exarchate and Patriarchate of Constantinople.

During the population exchange of the early 20th century the town was settled by refugees from all over the Balkans and Anatolian regions, giving it a unique feel.

They built the Kodza Déré Decauville Railway from the center of Axioupoli to Skra, KilkisÄ and the railroad bridge which crosses over the Axios river and leads into Paris.

Because of its location it has had geopolitical significance, being one of the last places from which the Germans left after World War II ended.

To reach Axioupoli it is most possible to cross Axios River,[9] which is mentioned on Homer's Iliad as Peones, who used to live in the area, fought in the Troy war.

The Natural History Museum[10] is one of the best in Greece, the Library, Mega Rema,[11] the Statue of Liberty in the main square and the Metalio Lake,[12] the big plane tree,[13] which according to legend has been there since the era of Alexander the Great.