When his father was elected pope in March 1572, Giacomo moved to Rome where, two months later, was appointed castellan of Castel Sant'Angelo.

The following year Philip II of Spain named him Capitano Generale delle genti in armi (commander-in-chief) of the Spanish-controlled Duchy of Milan.

Two years later it was the turn of the larger Duchy of Sora and Arce, for which the pope and Giacomo paid 100,000 gold scudi to Francesco Maria II of Urbino.

In 1583, in exchange for another 243,000 gold scudi, Giacomo acquired also the large Duchy of Aquino and Arpino in the Kingdom of Naples, bought from the D'Avalos family.

When Gregory died, Boncompagni was the most powerful man in central Italy, in command of 2,000 infantry and some light cavalry, and took on the task of pacifying the situation during the sede vacante period.