He was born in Florence, the son of Silvio Piccolomini Senior. Right after the election of Urban VIII he entered the circle of Cardinal Francesco Barberini, and in February 1625 was sent to the Catholic Court to announce its Legation. On his return from this trip, during which he accompanied the Legate, he was elected to the Archbishop See of Siena, which had become vacant on June 7, 1628, and went to take up the post on December 31 of that same year. He retired from the Archbishopric at the beginning of 1671, and moved to Rome, where he died on September 14 of the same year.

The Works of Galileo Galilei, national edition edited by Antonio Favaro, Florence, Barbčra, 1899-1909, vol. XX, Biographical Index, to v.