Francesco was raised in Florence as a noble at a time in which the city was captivated by the ruling body, the Medici family. He was taught to despise the middle-class, and also those who attempted to climb the social ladder, such as the Medici.
Throughout his early life, Francesco idly watched as the Medici bank eclipsed his own, and the government influence his family had held for centuries declined. With the downfall of his bank and loss of influence in the Florentine government, Francesco became angered and enraged with the Medici family in particular.
During this time, the Templar Grand Master Rodrigo Borgia offered Francesco a solution to his issues with the middle-class that would benefit both of them: kill the Medici. Francesco agreed, and began to plot his conspiracy.
However, in 1476, Francesco was accused of murder by Giovanni Auditore da Firenze. Giovanni was preparing to present his evidence in court, but was betrayed by Uberto Alberti, who was a secret ally of the Templars. Uberto had Giovanni and two of his sons, Federico and Petruccio, executed for the crime of treason. With Giovanni dead, there was no longer any evidence against Francesco, leading him to be cleared of all charges.
In 1478, Francesco met with a group of Templars at the southern gate of San Gimignano. The Pazzi family members, Jacopo, Francesco, and Vieri, met with Rodrigo Borgia. The group discussed their plan to overthrow the Medici dynasty, and to instate the Templars as the government of the city.
Francesco himself was tasked with organizing the Templar forces in Florence, and then sending word to his fellow conspirators when the time came to carry out the plans. However, after the meeting ended, Vieri remained in the city. Mario Auditore was aware of this, so he informed Ezio, and the two led an attack on the city. Mario led the mercenaries into the city, while Ezio made his way to Vieri, and assassinated him.
Later that year, Francesco met with another group of Templars in Florence in the catacombs under Santa Maria Novella. The group, Francesco, Jacopo, Rodrigo, Bernardo Baroncelli, and Stefano da Bagnone, talked about finalizing their plans to gain control of Florence and overthrow the Medici. The group joked about the Medici's arrogance and stupidity, but ensured Rodrigo that the plans would be carried out successfully. Once their discussion had finished, Rodrigo claimed that a new sun would rise over Florence the next morning, before leaving for Rome.
As planned, during high mass the next morning at the Duomo, Francesco and his co-conspirators attacked the Medici family. Francesco and Bernardo charged at Giuliano de' Medici, and stabbed him multiple times, killing him. Stefano also stabbed Lorenzo de' Medici, however he only was able to injure Lorenzo, as the Assassin Ezio Auditore entered the battle. Ezio fought off Francesco and his men, successfully defending Lorenzo. Francesco fled, and Ezio escorted Lorenzo back to his home to receive medical treatment.
- "You again? Why aren't you dead? Men! Slaughter him!"
- ―Francesco upon seeing Ezio on the rooftops.[src]
After bringing Lorenzo to safety, Ezio learned that Francesco was leading a battalion around the back of the Palazzo della Signoria, and began making his way there. Once there, Francesco greeted him from up on the prison ramparts, and ordered his men to kill the Assassin. However, Ezio evaded Francesco's men and made his way to the rooftops of the Palazzo.
Upon arriving on the rooftops, Ezio dispatched Francesco's guards while climbing to the top level where Francesco resided. Ezio then confronted Francesco, who cursed the Assassin and jumped off the top of the rampart, landing safely in a cart of hay.
Ezio followed Francesco over the rampart, and began chasing him through the Florentine streets. Ezio eventually caught up to Francesco though, and assassinated him. In his final words, Francesco merely claimed that everything was over with the failure of their conspiracy.
Later, Francesco's body was hung from the top of the Palazzo della Signoria by Medici supporters, which frightened Jacopo de' Pazzi, and caused him to flee from the city, knowing that their plans had failed.
Characteristics and personality
He was also confident and had much pride in himself and his fellow conspirators, claiming the Medici were too arrogant and too stupid to notice the plans being made against them. Francesco backed up this confidence by claiming to Rodrigo that no mistakes would be made in their plans.
Francesco was also violent and sadistic, stabbing Giuliano de' Medici multiple times after he was dead whilst yelling madly, demonstrating his desire to kill. Despite his violent behavior however, he fled when confronted by Ezio Auditore, and chose to run from the Assassin, rather than stay and fight.
There is also a hint that Francesco often ignored his son, Vieri, either intentional or not. It is stated in the letter from Fra Giocondo that Vieri often acted brashly and competed in competitions he had rigged in his favor merely to gain Francesco's attentions, hoping to win his approval. Francesco also seemed to show little remorse after his son's death, further suggesting that their relationship was not a strong one.
- Ezio: Now Firenze will judge you for what you've done.
- Francesco: It's over... It's all over...
- Ezio: Meglio essere felici in questa vita che aspirare a esserlo nella prossima. (Better to be content in this life, than aspire to it in the next) Requiescat in pace. (Rest in peace.)
- According to Vieri's date of birth, Francesco was 15 years old when his son was born.
- Historically, Francesco de' Pazzi was reputed to have stabbed himself in the thigh accidentally while killing Giuliano de' Medici in a frenzy. Although this doesn't actually happen in Assassin's Creed II, he does make such a mistake in the novel adaptation, Renaissance.
- When confronted by Ezio, Francesco jumps off the Palazzo della Signoria into a haystack for a quick escape. This is the only known example of a non-Assassin performing a type of Leap of Faith. 
- Francesco was the first character to whom Ezio gave his traditional "requiescat in pace" rites.
- He is briefly mentioned in a repressed memory during Assassin's Creed: Brotherhood along with his son.
- In Assassin's Creed: Revelations during the memory The Prince's Banquet, Ezio sings about Francesco and Vieri's deaths while disguised as a minstrel.