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The history of Vignanello begins in the ninth century BC, when it was home to a Villanovan settlement. It was then inhabited by the Falisci and Romans. With the Barbarian invasions, the inhabitants moved to the hill around a castle built by Benedictine monks. Vignanello is mentioned for the first time in some documents of Pope Gregory the Great.

Around 1170 it was removed from the Holy See by Frederick Barbarossa who gave it to Viterbo and then to the Prefects of Vico. In 1254 it was entrusted by Pope Nicholas III to the Orsini, but the death of the Pope returned Vignanello to the Vico. In 1445 Vignanello passed again under the control of the Church that gave it to several families of the time: Nardini, Doria, Orsini and Borgia.

Under the pontificate of Pope Clement VII, the fiefdom was given to Beatrice Farnese who was succeeded by her son, a member of the Sforza-Marescotti family. The Marescotti were succeeded by the Ruspoli who were the last owners.