Clerselier was a lawyer at the Parlement of Paris, paymaster general in Auvergne, and resident for the King of France in Sweden. He was the brother-in-law of Pierre Chanut, who married Clerselier's sister Marie-Marguerite and became a go-between for Descartes and Queen Christina of Sweden. He was also the brother-in-law of Jacques Rohault, one of Descartes’ followers, whom he hoped would marry one of his two daughters as a way of establishing links with his philosophical family.

Descartes and Clerselier met in Paris in 1644 and subsequently developed a close working relationship and friendship. With the Duc de Luynes, Clerselier translated the French edition of Meditations on First Philosophy (as Les méditations metaphysiques) (1647, republished in 1661). We also owe to him the revised Picot translation of the Principles of Philosophy for the fourth Paris edition of 1681, and the publication of Descartes’ correspondence in three volumes (1657, 1659, and 1667), arranged not in chronological order but by following an order of reasons that supported the reception of Cartesianism in the same period.

Generally speaking, Clerselier's choices, including his translation choices, show his strong desire to protect Descartes’ reputation after his death. Let us consider two examples of this. First, his posthumous publication of the Treatise on Man – accompanied by the Treatise on the Formation of the Fœtus (today known by the title Description of the Human Body), Louis de la Forge's Remarques, and the French translation of the preface to Florent Schuyl's Latin edition (1662) – offers a preface that highlights the real distinction of mind and body and Augustine's authority. Clerselier imports into the text of Treatise on Man (which Descartes wrote first) the metaphysical developments of the Meditations, which Clerselier considers to be first in the order of reasons and the only guarantee against an empirico-materialist interpretation of Treatise on Man. Second, Clerselier claims in the preface to the third volume of his edition of Descartes’ correspondence to have forged a letter to Gilles Personne de Roberval in which Descartes defends himself against the latter's attacks. This letter was read publicly on July 6, 1658, during a session of Louis Habert de Montmor's Académie; it comprised long excerpts from The World, which Clerselier did not edit until 1677, reestablishing the initial continuity between this work and chapter 8 of the Treatise on Man.