According to his account, the Paeonians trace their ancestry back to Axios.

Pelagon, the father of Asteropaeus, leader of the Paeonians at Troy, was born of the river god Axios and Periboea [Hom. Il. XXI, 139]. In early sources, the river is associated exclusively with the Paeonians, who, until the Macedonian advance in the 5^th century BC, inhabited almost its entire course. The Paeonian city of Amydon was also located in the river valley [Hom. Il. XVI, 287].

Along the A. River, especially along its lower course, are located remarkable settlements (the settlement mounds at Vardarophtsa and Vardina, Northern Greece) and necropoleis (Tsaoutsitza – Northern Greece, Gevgelija – Republic of North Macedonia, etc.) – evidence of life from the early Bronze Age onwards.

In ancient times, the river was an important communication artery, connecting the southern parts of the Balkan Peninsula with the Danube region and Central Europe through the Morava River valley. It is believed that during periods of demographic movement, the Axios valley was a route used for the movement of large groups of people.