The palace was one of the many mansions built by the Farnese in their domains. Initially, Villa Farnese had to have defensive characteristics as was common in the mansions of the Lazio region between the fifteenth and sixteenth centuries. The design for a fortified residence was initially entrusted to Antonio da Sangallo the Younger by Cardinal Alessandro Farnese il Vecchio. Work began in 1530, but was suspended in 1546 because of the death of Sangallo. Cardinal Alessandro the Younger wanted to resume the project of his grandfather, so, in 1547, gave the site to architect Jacopo Barozzi da Vignola and work resumed in 1559.