[3] His father was Pietro Mazzarini, and his mother was Ortensia Buffalini, a woman of a noble family of Città di Castello in Umbria, and a god-daughter of Filippo I Colonna, the Grand Constable of Naples.
In 1637 the Master General of the Order of Preachers, Niccolò Ridolfi, appointed Mazzarino as Vicar of the Province of Rome, and in April 1638 he was elected as Provincial.
At the suggestion of his brother Cardinal Mazarin, he was made Archbishop of Aix-en-Provence in 1645 by Pope Innocent X.
In October 1647 he was elevated to cardinal and in December of the same year was named as Cardinal-Priest of Santa Cecilia in Trastevere.
[1] In January 1648 he was appointed Viceroy of Catalonia and went to Barcelona, but fell ill and was forced to leave without formally taking up the post.