The first settlements in Chiusi dated to the late II millennium B.C., when villages of shepherds and farmers rose on the hills of the area

Chiusi, called Clevsin in ancient times, became one of the most important Etruscan cities, thanks to its very fertile alluvial soil and to its excellent land and water communication lines.

The city had its most flourishing period during the reign of Porsenna, the King who, at the end of the VI century B.C., besieged Rome for a short period of time. When the inhabitants of Chiusi got the Roman citizenship in 89 B.C., the city was fully embodied in the sphere of influence of Rome.

Its prosperity continued in the Imperial Age as well, when Chiusi, known as Clusium, remained a strategic passageway along the Roman consular road Cassia and the river Clanis which was navigable to the river Tiber. From the beginning of the III century A.D., Chiusi became an important site for the expanding Christian faith, as proved by the presence of the Catacombs St. Mustiola and St. Catherine and the St. Secondiano Cathedral.

During the following years, the city was a Lombard dukedom, which ended with a period of decline, and reached its worst decay when the region of Val di Chiana became a marsh. The complete reclamation of the area, during the XIX century, brought Chiusi back to its previous relevance.