Del Monte was the nephew of Antonio Maria Ciocchi del Monte, Archbishop of Manfredonia (1506–1511). When his uncle exchanged this see for a position as a Cardinal in 1511, Giovanni Maria Ciocchi del Monte succeeded in Manfredonia in 1512. In 1520, del Monte also became Bishop of Pavia. Popular for his affable manner and respected for his administrative skills, he was twice Governor of Rome and was entrusted by the papal curia with several duties. At the Sack of Rome (1527) he was one of the hostages given by Pope Clement VII to the Emperor's forces, and barely escaped execution. Pope Paul III made him Cardinal-bishop of Palestrina in 1536 and employed him in several important legations, notably as papal legate and first president of the Council of Trent (1545/47) and then at Bologna (1547/48).