Little is known about Nunes' early education, life or family background, only that he was born in Alcácer do Sal, his origins are Jewish and that his grandchildren spent a few years behind bars after they were accused by the Portuguese Inquisition of professing and secretly practicing Judaism. He studied at the University of Salamanca, maybe from 1521 until 1522, and at the University of Lisbon (this University later become the University of Coimbra) where he obtained a degree in medicine in 1525. In the 16th century medicine used astrology, so he also learned astronomy and mathematics.
He continued his medical studies but held various teaching posts within the University of Lisbon, including Moral, Philosophy, Logic and Metaphysics. When, in 1537, the Portuguese University located in Lisbon returned to Coimbra, he moved to the re-founded University of Coimbra to teach mathematics, a post he held until 1562. This was a new post in the University of Coimbra and it was established to provide instruction in the technical requirements for navigation: clearly a topic of great importance in Portugal at this period, when the control of sea trade was the primary source of Portuguese wealth. Mathematics became an independent post in 1544.
In addition to teaching he was appointed Royal Cosmographer in 1529 and Chief Royal Cosmographer in 1547: a post which he held until his death.
In 1531, King John III of Portugal charged Nunes with the education of his younger brothers Luís and Henry. Years later Nunes was also charged with the education of the king's grandson, and future king, Sebastian.
While at the University of Coimbra, future astronomer Christopher Clavius attended Pedro Nunes' classes, and was influenced by his works. Clavius, proponent of the Gregorian Calendar, the greatest figure of the Colégio Romano, the great center of Roman Catholic knowledge of that period, classified Nunes as “supreme mathematical genius". Nunes died in Coimbra.