He attended classes at the Collège d'Inville in Paris, where he subsequently became dean of the school.
Later on, he spent twenty years as an educator at the Collège du Cardinal-Lemoine in the Latin Quarter of Paris, and afterwards was professor emeritus at the University of Paris.
His textbook from 1779, De viris illustribus urbis Romae a Romulo ad Augustum, was still used in the 20th century by French students learning Roman history and Latin.
Other works by Lhomond include: In 1792 he was jailed for refusing to swear allegiance to the Civil Constitution of the Clergy, but was released shortly afterwards through intervention by Jean-Lambert Tallien (1767–1820), a former student of his at Collège du Cardinal-Lemoine.
A statue of Lhomond by French sculptor Eugène-Louis Lequesne stands in his home town of Chaulnes.