According to legend, the modern town was founded in the 5th Century A.D. by people fleeing from the pirate invasions down by the coast in the area called Le Murelle, where there was an Etruscan settlement (Regis) and later a Roman town (Regisvilla). Very little remains today of either, apart from the ruins of the port of Vulci, now under the sea.

The first documentary evidence for Montalto di Castro is dated 853 A.D. Due to its geographical position on the border of the Papal State, the town was seen as a strategic acquisition and thus fought over by many a noble family. This meant that the countryside suffered, the houses were abandoned and the population dwindled. With the defeat of the Vico family in 1359, the town passed to the Orsini family, then to a certain Angelo Ventura called the Tartaglia, the Aldobrandeschi family and finally the Church. Pope Martin V re-populated the area by issuing on 28th February 1421 a four-year pardon for those found guilty of offences against the Church. The lands began to be farmed again and homes built. In 1537 the Farnese family decided to add Montalto to the Ducato di Castro thanks to Pope Paul III. After the destruction of Castro in 1649 by Pope Innocent X, Montalto returned to the Church until 1870, when it was annexed to the Kingdom of Italy.