The first historical document, which refers to S. Casciano is from 1081 even though S. Maria "de Balneo" is defined as a paleochristian church of the diocese of Chiusi (4th – 5th centuries) and in the year 995 as the "cutis (de) Bagno" was donated to Abbazia di S. Salvatore by the marquis Ugo di Toscana. Orazio in one of his letters to Numonio Valla seems to allude to the therapeutic qualities of the waters of S. Casciano.
The use of the place name "Santo Cassiano" is first mentioned in documents of the monks of Abbazia S. Salvatore concerning a writ taken out the Emperor Enrico IV against the Aldobrandeschi family.
Around the middle of the 12th century the castle passed into the hands of the Viscounts of Campiglia and after being the object of contest between Orvieto and Siena, finally submitted to the rule of the latter at the end of the 1300s.
In 1559 it became part of the Grand Duchy of Tuscany.
The waters of S. Casciano have always been renowned, both in Roman times and during the medieval period, such that today the most important economic activities of the town are health tourism and agritourism.
The Commune of S. Casciano covers 91 sq km and other than the main town itself (582 m).
The treatment carried out at the small thermal establishment include mud therapy (non-regenerated natural mud), massage and inhalations. The town stands on a hillside and in the surrounding countryside, which contains some 42 springs, represents one of the most beautiful environments in southern Tuscany.
The building of most interest is the Chiesa Basilicale close to the hot springs and dating back to the year 1000. The bell-tower and portal are from the 11th to the 12th century. Inside the remains of early frescos are conserved.