[2] On 3 April 1519, Federico succeeded his father as Marquis of Mantua,[3] initially under the regency of his mother and his uncles Sigismondo and Giovanni Gonzaga.

Pope Leo X named him Captain General of the Church (commander in chief of the Papal Army) in July 1521, and he fought against the French at Parma in 1521 and at Piacenza in 1522.

[5] However, when Boniface, Marquis of Montferrat, died from a fall from a horse on 25 March of that year, Federico paid 50,000 ducats to Charles in exchange for the annulment of the contract, and pushed the pope for the restoration of his earlier marriage agreement.

[4] At the death of the last legitimate male heir of the Palaiologos family, Giovanni Giorgio (1533), the marquisate of Montferrat passed to the Gonzaga, who held it until the 18th century.

Like his parents, he was a patron of the arts; he commissioned the Palazzo Te, designed and decorated by Giulio Romano, as his summer palace just outside Mantua.