[2] His mother was the daughter of John, Margrave of Brandenburg-Kulmbach and Barbara von Sachsen-Wittenberg,[2] and the niece of Emperor Sigismund of the Holy Roman Empire.
Francesco was the first of the ten members of the House of Gonzaga to be given the red biretta of the cardinal and he was assigned to Santa Maria Nuova,[5] a church near the Via Sacra in Rome.
During the consistory celebrated at the basilica of St. Mark on 18 February 1471, Pope Paul II appointed him the Papal legate a latere [ Latin, “from the [ Pope's] side" ] to Bologna and at the same time Francesco was appointed Apostolic Commissioner for the Paternal States [ commissario apostolico per gli stati paterni ], with the authority to persuade their dioceses in favor of a crusade against the Turks, which was, however, not accomplished at that time.
During his stay in Rome, where he had by then made his home, Francesco, with Marco Cardinal Barbo, welcomed the new Duke of Ferrara, Borso d'Este.
For a while, it appeared that Gonzaga was about to be promoted to the rank of Archbishop but Jens Brostrup, who had already been elected by the Cathedral Chapter of Lund, managed to buy him out.
But he took the time to arrange and host a banquet in Bologna for the French ambassadors sent by King Louis XI to Pope Sixtus IV.
As the reward for the excellence of his services, the Cardinal of Mantua was granted in 1475 by the Pope the commendam of the deaconry of Sant'Agata dei Goti, a church on Via Mazzarino in Rome.
However, he was never made the Bishop of Bologna; that title went after his death to Giuliano Cardinal della Rovere, the future Pope Julius II.
But, before he could return to Bologna, he decided to go to Ferrara to encourage its residents to fight against the Republic of Venice, earning a reputation as a great orator.
Like other members of the family,[9] Francesco collected antiquities, including pieces of the treasures that belonged to Pope Paul II, himself a collector of gems.