He was the third son of Federico I Gonzaga, Marquess of Mantua.

He was the son of Frederick I of Mantua and commanded his brother Francesco II's troops before beginning his ecclesiastical career.

Pope Julius II was made a cardinal in the consistory of 1 December 1505.

[2] He was made apostolic administrator of Mantua from 1511 to 1521, finally resigning the post in favour of his nephew Ercole.

He gained much sympathy from the schismatic cardinals but remained faithful to Julius II.