Vermigli was born in Florence, Italy, on 8 September 1499 to Stefano di Antonio Vermigli, a wealthy shoemaker, and Maria Fumantina. He was christened Piero Mariano the following day. He was the eldest of three children; his sister Felicita Antonio was born in 1501 and his brother Antonio Lorenzo Romulo was born in 1504. His mother taught him Latin before enrolling him in a school for children of noble Florentines. She died in 1511, when Piero was twelve. Vermigli was attracted to the Catholic priesthood from an early age.