Amerigo Vespucci was born and raised in Florence on the Italian Peninsula. He was the third son of Ser Nastagio (Anastasio) Vespucci, a Florentine notary, and Lisabetta Mini. The father of Ser Nastagio (Anastasio) Vespucci had the name Amerigo Vespucci also.
Amerigo Vespucci was educated by his uncle, Fra Giorgio Antonio Vespucci, a Dominican friar of the monastery of San Marco in Florence. While his elder brothers were sent to the University of Pisa to pursue scholarly careers, Amerigo Vespucci embraced a mercantile life, and was hired as a clerk by the Florentine commercial house of Medici, headed by Lorenzo de' Medici. Vespucci acquired the favor and protection of Lorenzo di Pierfrancesco de' Medici who became the head of the business after the elder Lorenzo's death in 1492. In March 1492, the Medici dispatched the thirty-eight-year-old Vespucci and Donato Niccolini as confidential agents to look into the Medici branch office in Cádiz (Spain), whose managers and dealings were under suspicion.
In April 1495, by the intrigues of Bishop Juan Rodríguez de Fonseca, the Crown of Castile broke their monopoly deal with Christopher Columbus and began handing out licenses to other navigators for the West Indies. Just around this time (1495–96), Vespucci was engaged as the executor of Giannotto Berardi, an Italian merchant who had recently died in Seville. Vespucci organized the fulfillment of Berardi's outstanding contract with the Castilian crown to provide twelve vessels for the Indies. After these were delivered, Vespucci continued as a provision contractor for Indies expeditions, and is known to have secured beef supplies for at least one (if not two) of Columbus' voyages.
At the invitation of king Manuel I of Portugal, Vespucci participated as observer in several voyages that explored the east coast of South America between 1499 and 1502. On the first of these voyages he was aboard the ship that discovered that South America extended much further south than previously thought.