The Siege of Florence takes place from October 24, 1529 to August 10, 1530, at the end of the War of the League of Cognac.

A large Imperial and Spanish army under Philibert of Châlon, Prince of Orange and Pier Maria III de' Rossi surrounds the city, and, after a siege of nearly ten months, captures it, overthrowing the Republic of Florence and installing Alessandro de' Medici as the ruler of the city.The Florentines had thrown off Medici rule and established a republic after the Sack of Rome in 1527; the Florentine Republic has continued to participate in the war on the side of the French.

The French defeats at Naples in 1528 and Landriano in 1529, however, lead to Francis I of France concluding the Treaty of Cambrai with the Holy Roman Emperor Charles V. When Pope Clement VII and the Republic of Venice also conclude treaties with the Emperor, Florence is left to fight alone.

Charles, attempting to gain Clement's favor, orders his armies to seize Florence and return the Medici to power.The Republic resists this incursion; but, left without allies and betrayed by many of the mercenaries in her employ, Florence is unable to keep fighting indefinitely.

After the capture of Volterra by the Imperial forces and the death of Francesco Ferruccio at the Battle of Gavinana, further resistance becomes impractical, and the city surrendersin August 1530.