On 2 September 1637, at the age of 6, he inherited by her grandfather Alexander I's will the dominion of the Duchy of Mirandola,[1] receiving confirmation of the investiture in 1641 from Emperor Ferdinand III.

At the request of Pope Clement IX, he left Mirandola to Venice, from where he set sail the following month for the island of Crete with 9 warships and 3,000 soldiers.

After a stopover in Zakynthos, he landed in Candia on 23 August 1669 and joined the French, papal and Venetian forces in the Cretan War against the Ottomans, who had been besieging the Greek city for over twenty years.

He had a library and an art gallery set up, modernised the castle of the Pico family, and paved all the streets of Mirandola.

[2][3] Upon his death, he left the reign of the Duchy of Mirandola to his young nephew Francesco Maria II, entrusting its management to his sister Brigida Pico.