He was educated at the Seminary of Albano, and the La Sapienza University in Rome, where he received a doctorate in utroque iure (in both canon and civil law) on 4 June 1768.
He was appointed Prefect of the Congregation of Propaganda Fide on 24 May 1805, in addition to his duties in Jerusalem.
He was taken to France together with Cardinal Ercole Consalvi in December 1809 and banished to Semur-en-Auxois for not attending Napoleon's wedding with Maria Louise.
He was considered responsible, together with Bartolomeo Pacca, for Pope Pius VII's retraction of his agreement with Napoleon.
One of the most distinguished "black cardinals" (prohibited by Napoleon to wear red cardinalitial habit).