Born the son of a local government official in St. Lô, northern France, Le Verrier was educated at the Ecole Polytechnique and worked afterward on chemical problems with Joseph Gay-Lussac. He became a lecturer in astronomy at the Ecole Polytechnique in 1836 and succeeded Dominique Arago as director of the Paris Observatory in 1854.

Le Verrier worked on celestial mechanics, and in particular considered the problems associated with the motion of Uranus. In 1821 Alexis Bouvard, of the Paris Observatory, had published a set of tables of the motion of Uranus. Within a few years there was a noticeable discrepancy between the predicted and the observed position of Uranus. Assuming the correctness of Bouvard's work there were only two possibilities: either Newton's gravitational theory was not as universal as had been supposed, or there was an undetected body further out than Uranus but exerting a significant gravitational influence over its orbit. After much effort Le Verrier managed to deduce the mass and position that such a body would have to have to cause such disturbances in the orbit. (Le Verrier was unaware – as were most astronomers – that John Couch Adams had made these calculations in the previous year.) He asked Johann Galle in Berlin to search for the proposed planet. Galle was immediately successful, sighting Neptune on his first night of observation, 23 September 1846. The new planet was named Neptune and Le Verrier immediately became famous. He went into politics for a short time but wisely returned to astronomy in 1851.

Continuing with problems of celestial mechanics, Le Verrier reworked and revised much of the work of Pierre Simon Laplace. He discovered the advance of the perihelion (the point of the orbit nearest the Sun) of Mercury and was convinced that this anomaly was caused by an undiscovered planet between Mercury and the Sun. So confident was he of its existence that he named it Vulcan, but despite much searching Vulcan still remained undetected. (The discrepancies in the position of Uranus could be seen as an impressive vindication of Newtonian mechanics, but the true explanation of the anomalous motion of Mercury was to play a vital role in confirming Einstein's general theory of relativity.)

Camille Flammarion claimed that Le Verrier had never taken the trouble to look through a telescope at Neptune, being satisfied with his equations and the words of others.