It is one of I Borghi più belli d'Italia ("The most beautiful villages of Italy").

[3] According to the legend, Esus, the Celtic God of war, would be the origin of the name of the Esino river, on whose shores a town, Aesa, is presumed to have been founded in Roman times.

The first known document referring to Santa Anatolia dates from 1015, concerning the foundation of the monastery of Sant’Angelo by Conte Atto and his wife Berta.

Under the da Varano Santa Anatolia maintained a certain autonomy: the first collection of statutory norms dates from 1324.

The citadel remained immune from wars and pillages until 1443, when it was conquered by Francesco I Sforza.