By birth he was to be the successor of his father; Prince of Venafro, Venetian patrician, Marquis of San Martino, Count of Celano and Baron of Pescina.
However, he was also a nephew of Cardinal Alessandro Peretti di Montalto and a great-grand-nephew of Pope Sixtus V. As his father's only son he was urged to marry to continue the family line.
Little is known of his early ecclesiastic career but having served faithfully, he was elevated to cardinal on 16 December 1641 by Pope Urban VIII and was made Cardinal-priest of San Girolamo degli Schiavoni on 10 February 1642.
He was named Camerlengo of the Sacred College of Cardinals from 1653 to 1654 and participated in the Papal conclave of 1655 which elected Pope Alexander VII.
[2] Peretti was responsible for commissioning the Baroque facade of the Basilica of Sant'Andrea della Valle by Carlo Rainaldi which was started in 1655.