He fought for the imperial side in the Italian Wars; in 1524, in reward, he obtained by Charles V the county of Belgioioso, confiscated from the Barbiano family. Sent to defend the Spanish-controlled Kingdom of Naples, he however defected to the French in 1525, gaining Pope Clement V's enmity. After the Colonna had occupied Anagni, the Pope proposed to pardon him in exchange of stopping fighting against the papal lands: Colonna replied assaulting the papal palace in the Vatican City, forcing the pope to take shelter in Castel Sant'Angelo. Vespasiano and all his parents were therefore excommunication.
In 1527 he was reconciled with the pope thanks with the intercession of imperial ministers.
He died at Paliano in 1528.
- Litta, Pompeo (1835). Famiglie celebri d'Italia. Turin: Colonna di Roma.