d'Espagnat was born on 22 August 1921 in Fourmagnac, France, but spent most of his early years in Paris, where his father, a post-impressionist painter, and mother imbued him with a love of classic literature and the arts.

In 1939, as d'Espagnat made plans to enter the Ecole Polytechnique, World War II put his education on hold.

During this period he also worked with Enrico Fermi in Chicago, 1951–52, and on a research project led by Niels Bohr at the Institute in Copenhagen, 1953-54.

His first book, Conceptions of Contemporary Physics (1965), asked these questions and sketched possible resolutions, underscoring his insistence that scientists face the issues raised by their own pursuits.

Subsequently, d'Espagnat was an early interpreter of the deep philosophical significance of experimental research agendas in quantum physics.