He was appointed a cardinal at the age of 20. A few years after his elder brother, Duke Francesco IV, died in 1612 without heirs, he renounced the ecclesiastical career and succeeded his brother in both the Duchy of Mantua and the Duchy of Montferrat.
In 1616 he secretly married Camilla Faà di Bruno, whom he divorced in the same year. Their son Giacinto Teodoro Giovanni, although accepted at court, was not made Ferdinando's heir. He died of the plague—or was murdered—during the 1630 siege of Mantua. On February 16, 1617 he married Catherine de' Medici (1593–1629), the daughter of Ferdinand I, Grand Duke of Tuscany.
Ferdinand Gonzaga died in 1626. His younger brother Vincenzo II inherited the duchy.