Le Gentil first intended entering the Church and studied at the Collége de France. There he attended astronomy lectures of Delisle which caused him to turn to astronomy. He became assistent of Jacques Cassini at the Paris Observatory and participated in that man's geodesic surveys. Besides, he started to observe deepsky objects and discovered M32 in 1747 and (the nebula in) M8, M36 and M38 in 1749. These observations were presented to the Paris Royal Academy of Sciences in 1749 (Le Gentil 1749). Possibly, he discovered globular cluster NGC 6712 later that year.
In 1753 he was elected to the Royal Academy of Sciences in Paris.
On July 26, 1758, he summarized his observations and the knowledge of the Northern "nebulae" in a memoir presented to the French Royal Academy (Le Gentil 1759), just about one month before Charles Messier discovered his first nebula. In particular, he discussed the observations of various observers of the Andromeda Nebula and the Orion Nebula, and mentions some details on the catalog of De Chéseaux. Le Gentil's work was published in the volume of the Royal Academy for 1759, which was finally printed in 1765.
In March 1760, Le Gentil went on ship to sail from Brest on an expedition to observe the transit of Venus of June, 1761. British-French war prevented him from reaching his destination in Pondicherri, India, so that he missed the transit. He decided to prolong his journey until the next transit of Venus in 1769. After visiting numerous places in the Pacific and Indian Oceans, eventually he was ordered to return to Pondicherri, India for observing that event, but on the day of transit, June 3, 1769, the sky clouded over just for the duration of this phenomenon, so that Le Gentil also missed his second chance. His colleagues, who had stayed in Manila, Philippines, had an uninterupted view of the event.
Le Gentil returned to France in 1771. He published an account of his travel, A Voyage in the Indian Ocean, in two volumes in 1779 and 1781. He died in on October 22, 1792 at age 67.
Le Gentil was honored by naming Moon Crater Le Gentil (74.6S, 75.7W, 128 km diameter) in 1961.
Le Gentil discovered four or possibly five deepsky objects, including two original discoveries of M32, the companion of the Andromeda Nebula, and the nebula in M8, the Lagoon Nebula, and perhaps a third one, that of NGC 6712. Moreover he independently found M36 and M38, which both had been discovered previously by Hodierna.