The younger brother of Guidobaldo del Monte (1545-1607), Francesco Maria was born in Venice in 1549. He opted for an ecclesiastical career and was made a cardinal in 1588, after Grand Duke Ferdinando I (1549-1609) had turned down the position.

Cardinal del Monte was a lover of the arts and sciences, and was the patron of Caravaggio (1571-1610) during the period he spent in Rome. Together with his brother, he helped Galileo win a lectureship in mathematics in Pisa in 1589 and in Padua in 1592. In the wake of Galileo's successes in discovering the Medicean Planets, he gave the Cardinal a copy of his Sidereus nuncius [Starry Messenger] and a telescope as gifts. When Galileo went to Rome in 1611, Grand Duke Cosimo II (1590-1621) recommended him to the Cardinal's council so that he could be helped during his sojourn at the Vatican.

Francesco Maria del Monte was transferred in 1623 to the Diocese of Ostia. He died on August 17, 1626.