According to historians Cusano Mutri originated from the ancient Samnite city Cossa destroyed by the Romans along with Telesia. Certain news dates back to 490 A.D. when Pope Felice III sent a church official to officiate religious services in the chapel of the castrum. The presence of the Church in the area with the settlement of the Benedictines in Santa Maria del Castagneto around the eighth century, deeply influenced the culture and traditions of the Cusanese community.

In the countryside several settlements developed quickly and the influence of the church led to the construction of buildings of worship in each of them. The small inhabited centers formed a sort of ring that acted as a shield and ensured protection from brigands and Saracens. The urban center as it is today, was formed during the Norman monarchy that began a long phase of expansion of the inhabited nuclei merging them into a single community between the fifteenth and sixteenth. Over the years the small town has come under the control of several feudal lords.

Later, with Giuseppe Bonaparte who in 1806 took over the throne of the Kingdom of Naples, feudalism was abolished, closing a page of history lasting about 8 centuries. Although the Apennine area is at high seismic risk, the urban center of Cusano has remained intact over the centuries for geological reasons. It also withstood the devastating earthquake that struck the area on June 5, 1688, which completely destroyed the surrounding villages. For this reason the center of Cusano and its urban structure are very important for medieval scholars and for the most passionate visitors. The fortified urban nucleus rises on a rocky ridge that has leaded walls on the underlying plateau. Being the rocky ridge of not high width were not present in the village large squares but only the spaces where the streets slightly widened, commonly called widenings.