Marías was born in the city of Valladolid, but moved to Madrid at the age of five. He went on to study philosophy at the Complutense University of Madrid, graduating in 1936. Within months of his graduation the Spanish Civil War broke out. During the conflict Marías sided with the Republicans, although his actual contributions were limited to propaganda articles and broadcasts.

Following the end of the war in 1939, Marías returned to education. His doctoral thesis was rejected by the university, however, and handed over to the police, due to his inclusion of a number of lines critical of the rule of Franco. As a consequence of his writings Marías was briefly imprisoned and, upon his release, banned from teaching. Fortunately for Marías the proceeds from the sales of his History of Philosophy, which went through countless editions, meant that the punishment did not seriously damage his livelihood.

In 1948 he co-founded, along with his former teacher José Ortega y Gasset, the Instituto de Humanidades (which he went on to head after the death of Ortega in 1955). Between the late 1940s and the 1970s, being unable to teach in Spain, Marías taught at numerous institutions in the United States, including Harvard University, Yale University, Wellesley College, and UCLA.

Marías wrote on a wide variety of subjects during his long career. A subject of particular interest was Cervantes's Don Quixote. In 1964 he was elected into the Real Academia Española, and he won a Prince of Asturias award in 1996.

He is the father of novelist Javier Marías and art historian Fernando Marías, and married the sister of director Jesús Franco.