According to Pausanias, the settlement is named after king Amphilochos, son of Amphiaraus.

After the fall of Troy, Amphilochos settled in the area, which consequently was called Amphilochoi until the time of Pausanias.

[2] Under the Ottoman Empire, Ali Pasha of Ioannina, forcibly relocated residents of another village to the current location of the town and established a motel (serai in Turkish) to serve passing caravans.

It is linked with the GR-5 (E55 and E951, Antirrio - Messolonghi - Ioannina) and is also traversed by the GR-42 that serves Vonitsa, Preveza and the island of Lefkada.

Amfilochia is linked with the Ionia Odos, a toll road that bypasses the town itself.