While still a child, he was taken to Seville by his parents, who were Marranos. He studied philosophy at Alcalá de Henares and became teacher of metaphysics at the University of Salamanca. Later he devoted himself to the study of medicine, and became a popular practitioner in Seville, and physician in ordinary to the duke of Medina-Celi and to a family nearly related to the king.
When married and father of a family, De Castro was, at the instigation of a servant whom he had punished for theft, denounced to the Inquisition as an adherent of Judaism, and thrown into a dark and narrow dungeon, where he remained for three years, subjected to the most frightful tortures. As he persistently denied the charge, he was finally released, but compelled to leave Spain and to wear the sanbenito, or penitential garment, for two years. He thereupon went to Toulouse, where he became professor of medicine at the university, at the same time receiving from Louis XIV the title of councilor; but, weary at last of hypocrisy and dissimulation, he went to Amsterdam about 1666, and there made a public confession of Judaism, adopting the name "Isaac." In that city De Castro continued the practice of medicine, and soon became a celebrity, being elected to membership in the directory of the Spanish-Portuguese congregation and of several academies of poetry. He died at Amsterdam. Esther, his wife, died on July 5, 1712.
Orobio de Castro was a very prolific writer. His work entitled Certamen Philosophicum Propugnatæ Veritatis Divinæ ac Naturalis Adversus J. Bredenburgi Principia was published at Amsterdam, 1684 (reprinted 1703 and 1731). This work, in which De Castro attacks the Ethics of Spinoza, with whom he maintained a friendly correspondence, was translated into Spanish under the title Certamen Philosophico, Defiende la Verdad Divina y Natural Contra los Principios de Juan Bredenburg, by G. de la Torre, (The Hague, 1741). Certamen Philosophicum was translated into english in September 2020, by Walter Hilliger.
All the other writings of De Castro, like the foregoing translation, are still extant in manuscript. They are:
Long after De Castro's death a Jew by the name of Henriquez published an alleged work of his in French under the title Israel Vengé, claiming it to have been originally written in Spanish (London, 1770). It has been translated into English by Grace Aguilar (London, 1839).
De Castro's discussions on Christianity with the Dutch preacher Philipp van Limborch were published by the latter in the work entitled De Veritate Religionis Christianæ Amica Collatio cum Erudito Judæo, Amsterdam, 1687.
The various branches of this family are all of Spanish and Portuguese origin. Some have continued to bear the simple name of "De Castro", others are known as De Castro-Osorio; De Castro Sarmento; De Castro-Castello-Osorio; Pereira de Castro; De Castro Vieira de Pinto; Rodriguez de Castro; Orobio de Castro; De Castro de Paz; Henriquez de Castro, etc.
A separate article gives details of many more members of the family.