Established by a Napoleonic decree of October 18, 1810 as a branch of the "École Normale" in Paris, the Pisa Normale School began its activity of training secondary school teachers in 1813, and continued to operate during the restoration of the Lorraine Grand Duchy. The original denomination of "Normal School" indicated the primary educational function of the institute. The adjective "normal" was in fact used in the sense of "transmitting norms", and in the 19th century, teachers' training schools were called "Normal" schools for this reason.

The Normal School became a university of national standing in 1862, the year when the first "Annals of the Science Class" were published (starting in 1873, the "Annals of the Literature and Philosophy Class" were also published). In 1932 it officially acquired, along with administrational independence, the function of university institute for training in science and research. In addition to training secondary school teachers, the school was later assigned the function of training university professors and researchers. In addition to excellent laboratories, it has an outstanding library (around 600,000 volumes and 4,000 reviews). The largest core of the collection regards the scientific disciplines and those of the literature and philosophy classes.