The history of Neolithic settlements is documented by the discovery of several finds in the territory caves. The ruins of Hermitage of San Leonardo and of the castle overlooking the town testify the Byzantine presence in the 8th century.

During Norman-Swabian age, Isnello territory became royal property and the village grew around the castle. During Arab presence Isnello, which was called "Menyil al Himar" (fortified village), was included in Val Demone. At the end of the 12th century until half of the 15th century, during Angevin-Aragonese domination, the town history was bound to its alternating fuedal lords families: from Abbate to Filangeri, from Ventimiglia to Santacolomba; on 20 July 1453 Arnaldo Santacolomba, lord of Isnello, obtained from Alfonso the magnanimous the privilege of "Merum et Mixtum imperium", which is the right to enact laws.
In 1788 Isnello citizens, tired of supporting the domination exercised by the feudal lords, bought back the county lands, finally freeing themselves from baronial authority.

Adjacent municipalities
Castelbuono, Cefalù, Collesano, Gratteri, Petralia Sottana, Polizzi Generosa, Scillato