The municipality of St. Casciano has an origin which goes back to the Etruscan-Roman period. It takes its name from the famous thermal baths containing mineral sulphureous water. The Basilica Church, S. Leonardo's Colleggiata and St. Antonio's Oratorio can be also admired in St. Casciano.

The first built-up area originated with the arrival of the Etruscans.
The legend attributes the founding of the first thermal "baths", which were certainly used during the Roman period with the name of "Fonti Clusinii", to Chiusi' s king Porsenna. The baths were much appreciated by the Romans who also were interested in St. Casciano for its closeness to the Via Cassia, one of the most taken streets in the Imperial period to get northward from Rome.
Moreover, St. Casciano was one of the first centres to experience the arrival of Christianity. One first parish was already built in the V century and dedicated to St. Maria "ad Balneo".
Later, the area underwent a long process of depopulation because of its central position between the Barbarians' and the Byzantines' conflicting zones.
Historical traces of these clashes date to shortly before the year 1000. In 995 A.D., the "curtis in Bagno" was bought by the St. Salvatore abbots, whose authority was often renewed by imperial diplomas.
In 1226, one of Frederick II's acts established that the St. Casciano Castle had been handed over to the Campiglia Viscounts.
At the same time, the ancient Via Cassia became the Via Francigena, the main artery connecting the North of Europe with Rome which had previously been deviated nearer St. Casciano by the Longobards.
Villages like St. Casciano benefited from their closeness to this way to establish a trade-based economy characterized by accommodation activities.
The growth of the village was also due to the Campiglia Viscounts' diplomatic ability. They first were Ghibellines under Frederick Barbarossa and then Guelfs next to Orvieto and Florence. In this occasion, though, they were involved in the defeat of Montaperti which started the short period of domination on Tuscany by Siena.
With the division of the Viscounts into two branches in the XIV century, the family owning St. Casciano definitively fell under the influence of Siena. The Viscounts disappeared from the history of the town with the renunciation made by Giovanni, its last heir, in 1443. Militarily weakened, St. Casciano was attacked by Nicola Piccinino's Milanese troops (1455) and by Vitellozzo Vitelli's troops (1495).
In the XVI century, it was involved in the bloody conflict between Siena and the Spanish and Medicean troops, at the end of which it became part of the Tuscan Grand Duchy along with other Siena territories.
During the Grand Duchy period, the political stability favoured the recovery of the thermal activity which was further developed under Ferdinando I. Other remarkable works were carried out by the Grand Duke Pietro Leopoldo di Lorena who allocated a huge sum of money to re-establish the ancient Via Cassia after visiting the town in 1769, as he was interested in the recovery of the thermal heritage of the community. Nevertheless, the inadequacy of the thermal baths in comparison with those of other growing Tuscan cities did not allow a real recovery in this sector.