Vives was born in Valencia. As a child, he saw his father, grandmother and great-grandfather, as well as members of their wider family, executed as Judaizers at the behest of the Spanish Inquisition; his mother was acquitted but died of the plague when he was 15 years old. Shortly thereafter, he left Spain never to return.

He studied at the University of Paris from 1509 to 1512, and in 1519 was appointed professor of humanities at the University of Leuven. At the insistence of his friend Erasmus, he prepared an elaborate commentary on Augustine's De Civitate Dei, which was published in 1522 with a dedication to Henry VIII of England. Soon afterwards, he was invited to England, and acted as tutor to the Princess Mary, for whose use he wrote De ratione studii puerilis epistolae duae (1523) and, ostensibly, De Institutione Feminae Christianae, on the education of girls (a book he dedicated to the English queen, Catherine of Aragon).

While in England, he resided at Corpus Christi College, Oxford, where he was made doctor of laws and lectured on philosophy. Having declared himself against the annulment of the marriage of Henry VIII and Catherine of Aragon, he lost royal favour and was confined to his house for six weeks. On his release, he withdrew to Bruges, where he devoted the rest of his life to the composition of numerous works, chiefly directed against the scholastic philosophy and the preponderant unquestioning authority of Aristotle. The most important of his treatises is the De Causis Corruptarum Artium, which has been ranked with Bacon's Organon.citation needed

His most important pedagogic work are Introductio ad sapientiam (1524), De disciplinis, which stressed the urgent importance of more rationale programs of studying; De prima philosophia; and the Exercitatio linguae latinae, which is a Latin textbook consisting of a series of brilliantcitation needed dialogues. His philosophical works include De anima et vita (1538), De veritate fidei Christianae and De subventione pauperum (1526), the last dealing with social themes. Vives detected through philological analysis that the supposed author of the so-called Letter of Aristeas, purporting to describe the Biblical translation of the Septuagint, could not have been a Greek but must have been a Jew who lived after the events he described had transpired.

He died at Bruges in 1540 at the age of 48.

Vives imagined and described a comprehensive theory of education; he may have directly influenced the essays of Michel Eyquem de Montaigne. He was admired by Thomas More and Erasmus, who wrote that Vives "will overshadow the name of Erasmus."

Vives is considered the first scholar to analyze the psyche directly.citation needed He did extensive interviews with people, and noted the relation between their exhibition of affect, and the particular words and issues they were discussing. While it is unknown if Freud was familiar with Vives's work, historian of psychiatry Gregory Zilboorg considered Vives a godfather of psychoanalysis. (A History of Medical Psychology, 1941)

Vives taught monarchs. His idea of a diverse and concrete children's education long preceded Jean Jacques Rousseau, and may have indirectly influenced Rousseau through Montaigne. Vives altered classical rhetoric to express his own sort of pro-virginity half-feminism - which remains of interest to historians of gender. Among 16th century Spain's numerous "treatises for and against women," Vives "steers a middle path" (p. xxiv-xxv), neither misogynist nor sanctifying.

However influential he may have been in the 16th century, Vives now attracts minimal interest beyond specialized academic fields.