Although the first documentary evidence for the existence of this town dates back to the 9th Century A.D., Canino can boast a far longer history. Originally an Etruscan settlement, falling within the area of Vulci, then a strategic Roman town ruled by the noble Canina family.

In 1181 Pope Alexander III handed to town to Viterbo. In 1259, thanks to an alliance with Toscanella (modern-day Tuscania), it became an independent city state until Ludovic il Bavaro defeated it in 1327, destroying the city walls and killing most of the inhabitants in the process.
At the end of the 14th Century the town returned to the Church and was governed by Pope Ranuccio III Farnese. Under the Farnese family, Canino enjoyed peace and prosperity. The town expanded and in 1468 saw the birth of Alessandro Farnese, founder of the Ducato di Castro and the future Pope Paul III, the Pope of the great reforms.

Canino returned to the Church when the city of Castro was destroyed by Pope Innocent X in 1649. In 1808 it was sold to Luciano Bonaparte, the brother of Napoleon, who became known as the Prince of Canino. Under Bonaparte the malaria-stricken lands below Mount Canino were reclaimed and the Terme di Musignano were built, together with the castle of the same name.
In 1853, upon the death of Luciano Bonaparte, Canino was bought by the noble Torlonia family, who are still the owners of the mountain and the baths today, having handed the rest of the land to the Italian State under Mussolini.