He does not appear in the sources with official duties until on 6 February 1512, when his father, now ill and near death, decided to make him the city's ruler.
Upon election of Giovanni de Medici as Pope Leo X, Petrucci tried to maintain Siena's independence allying with the Kingdom of Spain in 1511.
Siena was wedged between the Republic of Florence and the Papal States, and maintained ties between Petrucci and the Baglioni of Perugia.
Leo X, unable to occupy the territories directly, facilitated a coup on 8 March 1516, by Raffaello Petrucci, Bishop of Grosseto and lord of Castel S. Angelo.
Borghese Petrucci was banished from Siena in May 1516 and moved to Naples, where, in the years following, he was named Baron.