Eventually he gave up the promises of a secular career and entered the service of the Catholic Church, in deference to the advice of Cardinal Pamphili whom he had met on a visit to Rome.

When that cardinal became pope as Innocent X, Casanate was made private chamberlain and soon advanced rapidly in the ecclesiastical career, becoming in turn Governor of Sabina, Fabriano, Ancona, and Camerino.

He was buried in the Basilica of St. John Lateran, though his heart was deposited in Santa Maria sopra Minerva, the church of the Dominicans, to whom he was always warmly attached, and who looked on him as their benefactor.

He also provided funds for a college (theologi casanatenses) of six Dominicans of different nationalities (Italian, French, Spanish, German, English, Polish) and two professors who would regularly lecture on texts by Thomas Aquinas, particularly the Summa Theologica.

To honour his friend, Cloche also had a statue of Casanate made by Le Gros which, in 1708, was placed outside the old entrance to the library but shortly later moved into the enlarged reading room.