The palace was constructed as a grand display of the wealth of its owner, Luca Pitti. However, the building was left incomplete when the man's money ran out and he died in 1472.
Sometime between 1481 and 1488, Girolamo Riario sent some of his men to ransack the Palazzo Pitti. These men killed some of the palace's residents and stole a valuable map, before returning to Girolamo in Forlì. Soon after, Lorenzo de' Medici contacted the Assassin Ezio Auditore da Firenze via pigeon coop while he was in Forlì, explaining to him what had had happened. With this knowledge, Ezio hunted down and killed Girolamo's men.
During the Bonfire of the Vanities, Girolamo Savonarola took up residence in the Palazzo after taking over Florence in 1494, and made it his primary residence. In 1498, however, after Ezio Auditore had severely thwarted the control Savonarola exerted on the populace, the people of Florence gathered in an angry mob in front of the Palazzo.
After trying to reason with the people, Savonarola eventually attempted to use his Apple of Eden to calm the mob, but Ezio used a throwing knife to make the monk drop the Apple. Powerless, Savonarola was finally captured by the Florentines and carried to the Palazzo della Signoria to be burned at the stake.
- Historically, Girolamo Savonarola lived in the Chiesa di San Marco, or Church of San Marco, after he took over Florence. The Palazzo Pitti would still have been in the possession of the Pitti family at the time.