The Scuola Normale Superiore was founded in 1810 by Napoleonic decree, as twin institution of the École Normale Supérieure in Paris, itself dating back to the French Revolution jurisdiction. The term “École Normale” (“Scuola Normale”) was coined by Joseph Lakanal who, in submitting a report to the National Convention of 1794 on behalf of the Committee of Public Instruction, explained it as follows: “Normales : du latin norma, règle. Ces écoles doivent être en effet le type et la règle de toutes les autres”.

Napoleon I rethought the project of an École Normale in 1808, by establishing a “Normale” hall of residence in Paris, to house young students and train them in the art of teaching the humanities and sciences. The project was replicated in Tuscany by a decree dated 18 October 1810, with the foundation in Pisa, seat of one of the Imperial University Academies, of a branch of the École Normale Supérieure of Paris, called the Scuola Normale Superiore.

When, in 1814, Ferdinand III, Grand Duke of Tuscany returned to Tuscany, the project of a Scuola Normale in Pisa ceased. Only at the beginning of the 1840s, in connection with the university reform of 1839-1841, was the project resumed. The question was combined with the proposals of resumption of the educational activities of the ancient Order of Saint Stephen, whose main premises were within the Palazzo della Carovana in Pisa. On 28 November 1846, a grand-ducal motu proprio founded a Tuscan Scuola Normale in Pisa (also referred to as the Imperial Royal Scuola Normale, since it was linked to the Austrian system), with both theoretical and practical aims, under the patronage of the Order of Saint Stephen, but depending on the University of Pisa.
On 17 October 1862 the Minister of Education of the Kingdom of Italy Carlo Matteucci implemented new regulations in a decree that transformed the institution to the famous "Normal School of the Kingdom of Italy". There was to be an organic division into two Faculties, of Arts and Sciences.

In 1863, was appointed a new Director of the Scuola Normale, the respected Pasquale Villari. Villari left the Scuola in 1865, and his place was taken by the mathematician Enrico Betti; from 1890 to 1900, the position of Director was filled by literature historian Alessandro d'Ancona, and from 1900 to 1918 by the mathematician Ulisse Dini. The new regulations, issued by Minister Michele Coppino in 1877, reviewed and simplified the internal study regulations and equalized, from an organizational point of view.

The philosopher Giovanni Gentile, was placed at the head of the Scuola Normale as commissioner in 1928 and as director in 1932. He expended the premises of the Scuola Normale, Palazzo dei Cavalieri, and also promulgated a new statute in 1932, which recognized the Scuola Normale as an advanced education institute with “a legal status and administrative, educational and disciplinary autonomy”, insuring an autonomy from the University of Pisa. Further, he reformed the Scuola, gave it formal autonomy and sought an expansion to other disciplines, with the creation of the Collegio Mussolini per le Scienze Corporative (1931) and the Collegio Nazionale Medico (1932). The new colleges were later merged in the Collegio Medico-Giuridico, which continued to operate (in the fields of law and medicine) under the jurisdiction of the Scuola Normale Superiore di Pisa.

During the post-war period, there were many practical difficulties; however, besides the restoration of Palazzo dei Cavalieri. Scuola Normale in 1951, established the Antonio Pacinotti boarding school, reserved to students of the faculties of Agriculture, Economics and Engineering, with plans to be further opened to other faculties as well. In 1967 the Scuola Superiore di Studi Universitari e Perfezionamento merged the Scuola per le Scienze Applicate A. Pacinotti (founded in 1951) and the Collegio Medico-Giuridico forming the Sant'Anna School of Advanced Studies. The new institution, while still committed to the model established by the Scuola Normale Superiore di Pisa, was administered by the University of Pisa. In 1987 Sant'Anna School of Advanced Studies acquired complete independence (Law of 14 February 1987, No.41) and maintains strong ties with both the Scuola Normale Superiore di Pisa and the University of Pisa creating the Pisa University System.

Over time, the Scuola Normale has increasingly opened up to society, and while remaining an elite institute, has offered its cultural activities and heritage to an ever-wider audience. Also, thanks to the law of 18 June 1986, which granted the Diploma di Perfezionamento equivalent to Doctor of Philosophy, the Scuola Normale has been given separate university status by the Ministry of Education, Universities and Research (Italy), together with Sant'Anna School of Advanced Studies leading the model of Scuole di Eccellenza (Schools of Excellence or Superior Graduate Schools in Italy) or Scuola Superiore Universitaria.