In 1944, Hadot was ordained, but following Pope Pius XII’s encyclical Humani generis (1950) left the priesthood. He studied at the Sorbonne between 1946–1947. In 1961, he graduated from the École Pratique des Hautes Études. In 1964, he was appointed a Director of Studies at EPHE, initially occupying a chair in Latin Patristics, before his chair was renamed "Theologies and Mysticisms of Hellenistic Greece and the End of Antiquity" in 1972. He became professor at the Collège de France in 1983, where he assumed the chair of the History of Hellenistic and Roman Thought. In 1991, he retired from this position to become professeur honoraire at the collège; his last lecture was on 22 May that year. He concluded his final lecture by saying, "In the last analysis, we can scarcely talk about what is most important."
Hadot was one of the first authors to introduce Ludwig Wittgenstein's thought into France. Hadot suggested that one cannot separate the form of Wittgenstein's Philosophical Investigations from their content. Wittgenstein had claimed that philosophy was an illness of language and Hadot notes that the cure required a particular type of literary genre.
Hadot is also famous for his analysis of the conception of philosophy during Greco-Roman antiquity. He identified and analyzed the "spiritual exercises" used in ancient philosophy (influencing the thought of Michel Foucault in the second and third volumes of his History of Sexuality). By "spiritual exercises" Hadot means "practices ... intended to effect a modification and a transformation in the subjects who practice them. The philosophy teacher's discourse could be presented in such a way that the disciple, as auditor, reader, or interlocutor, could make spiritual progress and transform himself within." Hadot shows that the key to understanding the original philosophical impulse is to be found in Socrates. What characterizes Socratic therapy above all is the importance given to living contact between human beings.
Hadot's recurring theme is that philosophy in Antiquity was characterized by a series of spiritual exercises intended to transform the perception, and therefore the being, of those who practice it; that philosophy is best pursued in real conversation and not through written texts and lectures; and that philosophy, as it is taught in universities today, is for the most part a distortion of its original, therapeutic impulse. He brings these concerns together in What Is Ancient Philosophy?, which has been critically reviewed.