The settlement of Castro was founded in prehistoric times, and was later the seat of an unspecified Etruscan city, probably Statonia. In the Middle Ages it had a castle (Latin: "castrum"), hence the name. Although an autonomous commune, it remained nonetheless under papal suzerainty. In 1527 a pro-independence faction assumed power, but they were later ousted by Pier Luigi Farnese, whose family was to rule Castro until the 17th century. In the same year another Farnese, Gian Galeazzo, sacked it in the wake of the Sack of Rome.