Maupertuis, who was born at Saint-Malo in northwest France, joined the army as a youth, leaving in 1723 to teach mathematics at the French Academy of Sciences in Paris. He traveled to England in 1728 where he became an admirer of Isaac Newton's work and was made a member of the Royal Society of London. He was responsible for introducing Newton's theories on gravitation into France on his return.

In 1736 Maupertuis led an expedition to Lapland to verify Newton's hypothesis that the Earth is not perfectly spherical by measuring the length of a degree of longitude. This was successful and as a result Maupertuis was invited by Frederick the Great to join his Academy of Sciences in Berlin.

Maupertius is best known as being, in 1744, one of the first to formulate the principle of least action, which was published in his Essai de cosmologie (1750; Essay on Cosmology). A similar principle had previously been formulated by Leonhard Euler as a result of his mathematical work on the calculus of variations, whereas Maupertuis had been led to formulate his version of the principle through his work in optics. In particular Maupertuis's attention was drawn to the need for such a principle by his interest in the work of Willebrord Snell and Pierre de Fermat. Fermat had shown how to explain Snell's law of refraction, which describes the behavior of a ray of light at the boundary of two media of different densities on the assumption that a ray of light takes the least time possible in traveling from the first medium to the second. However, Fermat's explanation implied that light travels more slowly in a denser medium and Maupertuis set out to devise an explanation of Snell's law that did not have this, to him, objectionable consequence. Maupertuis thought of his principle as the fundamental principle of mechanics, and expected that all other mechanical laws ought to be derivable from it. He attempted to derive from his principle a proof of the existence of God.

Maupertuis was not a mathematician of Euler's stature and his version of the principle was not as precisely formulated mathematically. However, his attempts to apply it to a much wider range of problems made it an influential formative principle in 18th- and 19th-century physical thinking. Joseph Lagrange, in his work on the calculus of variations, dispensed with the teleological and theological trimmings Maupertuis had given the principle and found wide application for it in mechanics. Subsequently the principle became less influential until it was revived and refined by William Hamilton.

Maupertuis, who had a quarrelsome character, became involved in violent controversy over the principle. Samuel König, another scientist at Frederick's court, claimed that it had been formulated earlier by Gottfried Liebniz. Maupertuis found himself on the receiving end of some of Voltaire's most biting satires, and eventually he was hounded out of Berlin.