In the time of Pope Gregory XIII, he acted as papal secretary of state (in office 1572 to 1585), having a key role in the curia. He built the Villa d'Este, in his birthplace Cernobbio, in 1568, as a summer residence; and the Palazzo Gallio of Gravedona. He was bishop of Martorano in 1560, archbishop of Manfredonia in 1562, bishop of Albano in 1587, bishop of Sabina in 1589, bishop of Frascati in 1591, bishop of Porto e Santa Rufina in 1600, bishop of Ostia in 1603.