Toletus was born in Spain into a family of humble origins, probably of Jewish or Moorish descent. He studied philosophy at Zaragoza or Valencia and theology at Salamanca. His professor of theology, Domingo De Soto, characterized him as an intellectual prodigy, and, indeed, by age fifteen Toletus held a chair in philosophy (Campbell 1921, 112–13). He entered the Jesuit order in 1558 and taught at the prestigious Collegio Romano in Rome, where future Jesuit teachers were trained. From 1559 to 1562 he taught philosophy there, and from 1562 to 1569, theology. From 1571 onward he was sent on various diplomatic missions, including one in 1596 to convert Henry IV of France (Schmitt and Skinner 1988, 838). Toletus became the first Jesuit cardinal in 1593 (Van Ackeren 2003, 102). His accomplishments were both political and intellectual. In 1595 he persuaded Pope Clement to grant Henry IV absolution, which established peace in France (Campbell 1921, 113). He also left behind numerous writings, including influential commentaries on Aristotle's Physics, De Anima, and De Generatione et Corruptione and on Saint Thomas's Summa Theologiae (Schmitt and Skinner 1988, 838).

Descartes was familiar with at least some of Toletus's works. On September 20, 1640, he wrote to Marin Mersenne, expressing a desire to reacquaint himself with the Scholastic philosophy of his youth in anticipation of objections to his Meditations on First Philosophy. Enlisting Mersenne's help, Descartes writes, “I only remember some of the Conimbricenses, Toletus and Rubius” (AT III 185, CSMK 154). While we do not know exactly which textbooks Descartes studied at the Collège de la Flèche, Toletus's Commentary on Aristotle's Physics is fairly representative. In standard commentary format, it follows the order of the Latin edition of Aristotle's Physics, which was divided into books, chapters, and texts. Toletus gives a comprehensive explanation of each text and then handles some standard questions. He usually gives a complete overview of all the opposing positions on a certain issue but summarizes the arguments very concisely rather than giving details.

See also Conimbricenses; Jesuit; Rubius, Antonius; Scholasticism