Le Chatelier was born in Paris, the son of the inspector-general of mines for France. He himself began studying mining engineering, before becoming professor of chemistry at the School of Mines in 1877. He later became professor of mineral chemistry at the Collège de France and finally took the chemistry chair at the Sorbonne in 1907.

He was particularly interested in metallurgy, cements, ceramics, and glass, and his studies of flames led him to study heat and its measurement.

He made a number of contributions to thermometry, the most important of which was his first successful design of a platinum and rhodium thermocouple for measuring high temperatures (1887). This was based on the principle shown by Thomas Seebeck in 1826 that if a circuit is made from two different metals and heated, a current will flow, and that the current is proportional to the temperature difference between the junctions. It was quickly appreciated that the Seebeck effect could be used in a variety of measuring devices; if one junction was placed on the object to be measured and the other kept at a known constant temperature then the first temperature could be calculated by measuring the current. By using platinum and platinum–rhodium alloy rods, Le Chatelier succeeded where many others had failed.

His most important discovery, Le Chatelier's principle, was made in 1884. This simply states that any change made in a system of equilibrium results in a shift of the equilibrium in the direction that minimizes the change. In his original 1884 version he referred only to pressure but soon generalized the principle to cover any kind of external constraint. Le Chatelier published his principle in 1888 as the Loi de stabilité de l'equilibre chimique (Law of Stability of Chemical Equilibrium). The principle is important in studies of chemical equilibrium for predicting the effects of pressure and temperature on an equilibrium reaction.

Le Chatelier's principle fitted in well with the law of mass action recently formulated by Cato Guldberg and Peter Waage and the new chemical thermodynamics of Josiah Willard Gibbs, whose work Le Chatelier was responsible for introducing to France. The principle was soon shown to have industrial implications, for Fritz Haber successfully utilized it in his process for the production of ammonia.