Since 1969 the Lycée Saint-Louis has had the particularity of offering only preparatory classes for admission to the grandes écoles and no high-school classes (i.e. classes leading to the baccalauréat, the required qualification to enter university in France). The same does not apply to rival and equally prestigious and elitist schools (e.g. Louis-le-Grand, Henri IV, Janson de Sailly, etc.) nor to any other school offering preparatory classes. Just under 500 students graduate from the Lycée Saint-Louis annually and are admitted to one of the grandes écoles. The school has a total of over 1,300 students, 350 of whom are full boarders (both men and women).

  Although Saint Louis' patronage dates back to 1820, the school has a much longer history. It was founded as the Collège d'Harcourt in 1280 on the same site that it currently occupies. At the time it was on the outskirts of Paris; today it is in one of the most central parts of the city. Originally a boarding school for students of the "nation" of Normandy, the Collège d'Harcourt subsequently imparted education in which Aristotle had pride of place. At that stage it was a theological and scientific school for training high-ranking scholars and academics. Gradually the recruitment of students spread to provinces other than Normandy and statuses other than boarders on scholarships. In the sixteenth century, following Henri IV's reforms to the university system, the Collège d'Harcourt became an educational institution training cultivated minds destined for a wide range of careers. Racine, Boileau and, later, Charles Perrault, Saint-Evremond, Abbé Prévost, Diderot and Talleyrand all studied at the Collège d'Harcourt. During the seventeenth and eighteenth centuries opposition to the Jesuits, especially of the Collège de Clermont (Louis-le-Grand) situated a few streets away, occupied Harcourt's headmasters, teachers and even students who wrote arguments against their neighbours as part of their coursework. In 1793 the school's history was interrupted when, by decree of the Convention, it was closed down. Its premises were used for various purposes: a prison for victims of the Terror, barracks, the seat of the Académie de Législation, a reformatory for young prisoners, and accommodation for students of the École Normale.

  In 1812 Napoleon ordered a high school to be established on the site and in 1820 the Collège d'Harcourt opened its doors again under the name Collège Royal Saint-Louis and then Lycée Saint-Louis from 1848. Baudelaire, Gounod, Pasteur, Zola, Labiche and Saint-Exupéry were all students of the school. In the latter half of the nineteenth century, until the 1920s, the architecture of the establishment changed profoundly. With the construction of the Boulevard Saint-Michel, started in 1860, the school had to move back and reconstruct its façade. The École des Mines was likewise forced to demolish two wings of the Hôtel Vendôme built from 1840 to 1852. The Lycée Saint-Louis subsequently bought the adjacent land and houses, along the new Boulevard Saint-Michel and the Rue Monsieur-le-Prince, and a new wing was built along the Rue Racine. In the 1840s the Collège d'Harcourt's tradition of a literary education started to wane. The school's teaching was gradually and eventually entirely devoted to scientific subjects and preparatory classes for the grandes écoles, the first of which were opened in 1866. Nobel prize-winners for physics, Pierre-Gilles de Gennes (1991) and Georges Charpak (1992, also an École des Mines de Paris graduate) both studied at the Lycée Saint-Louis.