Heir of a rich family of merchants and revenue officers owning commercial companies in Lyon and Antwerp, he was educated under the influence of the Dominican uncle Fra Pacifico, disciple of Savonarola.
From 1529, after his father's death, he dedicated himself to the city political life leaving the business's management to his brothers. He fulfilled numerous public assignments.
He dealt with the Straccioni riots, negotiating with the rebellious and repressing their movement.
In 1533 he was elected Gonfaloniere for the first time. He cultivated historical and literary interests.
He organized a conspiracy against Cosimo de Medici, inspired in 1544 by the reading of the “Vite” of Plutarco. Burlamacchi planned to march with the mountains' troops, of which he had the command against Pisa, to provoke a rebellion against Florence and to reach the city agitating the people and the cities which were under the Medici government.
With the liberation of Tuscany from the tyranny, he constituted a federation between the independent cities under the protection of the emperor.
Francesco Burlamacchi went to Venice in the April in 1546 to find the help of Leone Strozzi and decided not to execute the plan before September.
In the meantime he was elected Gonfaloniere for the second time in July-August. Some tip-off to the Duke Cosimo de Medici and to the government of Lucca exposed his plan. He was immediately arrested in the Elders' palace, when he still was the Gonfaloniere. It started a disagreement with Florence, who wanted the conspirator delivered there. The people of Lucca decided to protect their city, giving the prisoner to the emperor Carlo V only and supporting the mental illness theory to diminish the importance of the subversive plan. The emperor put him to death in Milan on the 14th of February in 1548.In the XIX century Francesco Burlamacchi was considered one of the pioneer of the National Resurgence and with the Italian unity his memory was honored with a statue in the San Michele in Foro square.