[4] Durazzo took up a career in the administration of the Papal States: in 1621 he became referendary of the Tribunals of the Apostolic Signature thanks to the support of the seven cardinals of the Republic of Genoa.

[3] Stefano Durazzo was created cardinal Priest on 28 November 1633 with the title of San Lorenzo in Panisperna.

[5] His government of the Archdiocese of Genoa was from the very beginning marked by his conflicts with the aristocracy, represented by the Senate of the Republic, and also with a large portion of the clergy .

In particular Durazzo opposed the claim of the Doge to receive regal honors, disputed with the Senate over the control of hospitals, and ordered to the clergy the mandatory use of clerical clothing.

[6] Another important reason of his conflict with the ancient aristocracy of the town was his subtle pro-France attitude[5] which he shared with Pope Urban VIII, who made him cardinal, and with the Barberini family.

During the First War of Castro he closed the doors of Bologna and did not attack the army of Odoardo Farnese, saving the town but actually opposing the Barberini and the pope.

[4] Returned in Genoa, he celebrated a synod in April 1643 which resulted in a turn of the screw against the laxity of the clergy.