Evidence of human presence in the area dates from the Neolithic age, but probably the city proper was founded in the 7th century BC when the acropolis on St. Peter's Hill was surrounded by a line of walls.

After the defeat of the coastal cities by the Greeks (4th century BC), Tuscania also became a maritime trade centre through the port of Regas (next to today's Montalto di Castro).

During the struggle between the Guelphs and Ghibellines throughout the Holy Roman Empire, it was captured by Frederick II of Hohenstaufen on March 2, 1240, and provided with a line of walls.

A failed military expedition against Pope Boniface VIII (early 14th century), led to the submission to Rome, with the pejorative name of Tuscanella.

In 1495 it was ravaged by the French troops of King Charles VIII during his march towards the Kingdom of Naples, much thanks to the destruction of the walls ordered by Cardinal Giovanni Vitelleschi in reply to the continual internecine struggles and public riots.

The main attraction of the city is the Church of San Pietro, built in Lombard-Romanesque style, begun in the year 739[5] and renovated in the 11th–12th centuries.

The interior has a nave and two aisles divided by low columns and pilasters incorporating half-columns, with antique and mediaeval capitals.