The naturally strategic position of the town (unapproachable from three sides due to the steep tuff cliffs) has meant that it's been continuously populated since Etruscan times. Linked to the fortunes of the city of Vulci, Tessennano became a backwater after the Roman invasions in 280 B.C.

The name Tessennano first appeared officially in a tomb from the 3rd - 2nd B.C. and found in 1956, though no other traces exists until the Middle Ages when the town walls were built. In 1102 the town was handed to the Church by Matilde di Canossa and the in the 13th Century part of the land was given to nearby Tuscania. The remaining lands were offered to a certain Nerio de Turri by Pope Boniface VIII.
By 1464 the entire territory belonged to the powerful Farnese family. Like Arlena and Piansano, families from Allerona in Umbria moved in to re-populate the area (malaria had taken its toll). The town expanded in the area known as Sodo, adding the older centre that the locals call Dentro (i.e. inside the old town walls). In 1537 it became part of the Ducato di Castro under Pope Paul III, becoming linked to the fortunes of Castro until the destruction of that town in 1649. In 1659 Tessennano returned to the Church, being governed by various local families until the Marquis Battista Casali Patriarca bought the castle in 1778 from Pope Pius VI, though they never actually resided here.