Mesland was born at Orléans and died at Santa Fe, Bogotá. He was a Jesuit, becoming a novitiate in Paris and studying rhetoric there, 1630–33. He then took the course in philosophy, 1633–36, at the Collège Henri IV, the Jesuit school in La Flèche Descartes had attended; he taught letters and studied theology there, 1636–46. His correspondence with Descartes began in 1644, after he informed Descartes that he wrote an abridgment of the Meditations in a form that would be fit for teaching students at a Jesuit college. Descartes was delighted, believing that the paraphrase would be effective for getting it approved (AT IV 122, CSMK 236). The correspondence ended in 1645, when Mesland left La Flèche to become a missionary in the New World.

The Mesland correspondence directly addresses the theologically sensitive topic of the nature of human freedom: whether our freedom of action involves an “indifference” that allows our will to act otherwise than it does. Jesuits insisted that such indifference is needed to ward off the Calvinist doctrine of predestination, and others argued that it would compromise the Augustinian doctrine that meritorious action follows from God's irresistible grace. Descartes seems to have favored different sides at different times. Early on he stated that his account of freedom agreed perfectly with the one written by the Sorbonne Oratorian Guillaume Gibieuf (AT I 153, CSMK 26). He insisted in the Fourth Meditation that “the indifference I experience when there is no reason moving me more in one direction than in another is the lowest grade of freedom,” and that our will is most free when it is led to embrace the true and the good either by clear and distinct perception or by divine grace (AT VII 57–58, CSM II 40). However, in a 1644 letter, presumably to Mesland, Descartes claimed that there is only “a verbal difference” between Mesland's position and his own since, according to him, our free action involves “a real and positive power to determine” that action (AT IV 116, CSMK 234).