The University of Pisa was officially established on September 3, 1343. However, a number of scholars claim its origin dates back to the 11th century.The first reliable data on the presence of secular and monastic schools of law in Pisa is from the 11th century and the second half of the 12th century, a time when Pisa had already achieved a remarkable economic development. The following century formed the first documents to prove the presence of doctors of medicine and surgery.
The earliest evidence of a Pisan Studium dates to 1338, when jurist Ranieri Arsendi transferred to Pisa from Bologna. He, along with Bartolo da Sassoferrato, a lecturer in civil law, were paid by the municipality to teach public lessons. The papal bull In supremae dignitatis, granted by Pope Clement VI on September 3, 1343, recognized the Studium of Pisa as a Studium Generale; an institution of further education founded or confirmed by a universal authority, the Papacy, or Empire. Pisa was one of the first European universities to boast this papal attestation, which guaranteed the universal and legal value of its educational qualifications.
The first taught subjects were theology, civil law, canon law and medicine. In 1355, Francesco da Buti, the well-known commentator of Dante's Divine Comedy, began teaching at the Studium. Pisa and its Studium underwent a period of crisis around the turn of the 15th century: the Florentines' conquest of the town led to the university's closure in 1403. In 1473, thanks to Lorenzo de Medici, the Pisan Studium resumed its systematic development, and the construction of a building for holding lessons was provided for in 1486. The building — later known as Palazzo della Sapienza (the "Building of Knowledge") — was located in the 14th-century Piazza del Grano. The image of a cherub was placed above the gate Dell'Abbondanza (the "Gate of Abundance"), leading to the piazza, and today is still the symbol of the university.
Following the rebellion and the war against Florence in 1494, the Pisan Studium suffered a period of decline and was transferred to Pistoia, Prato and Florence. The ceremonial reopening of the university on November 1, 1543, under the rule of Duke Cosimo I de Medici, was considered as a second inauguration. The quality of the university was furthered by the statute of 1545 and the Pisan Athenaeum became one of the most significant in Europe for teaching and research. The chair of Semplici (botany) was held by Luca Ghini, founder of the world's first botanical gardens. He was succeeded by Andrea Cesalpino, who pioneered the first scientific methodology for the classification of plants, and is considered a forerunner in the discovery of blood circulation. Gabriele Falloppio and Marcello Malpighi lectured in anatomy and medicine. Galileo Galilei, who was born and studied in Pisa, became professor of mathematics at the Pisan Studium in 1589.
The annexation of Tuscany to the Napoleonic Empire resulted in the transformation of the Studium into an Imperial Academy. The Athenaeum became a branch of the University of Paris, and the courses and study programs were structured following the French public education model. Five new faculties were established: (theology, law, medicine, science and literature), along with examinations, different qualification titles and graduation theses. In 1810 the scuola normale was established, after the École normale of Paris.
The Restoration wasn't able to cancel the effects of the Napoleonic experience. The first Congress of Italian Scientists was held in Pisa in 1839. Over 300 experts of various disciplines and 421 scientists discussed zoology, comparative anatomy, chemistry, physics, mathematics, agronomy, technology, botany, vegetation physiology, geology, mineralogy, geography and medicine. In 1839–1840, the Director of Education Gaetano Giorgini brought about the most important reform in the University of Pisa by raising the number of faculties to six (theology, law, literature, medicine, mathematics, and natural sciences). Giorgini also created the world's first chair of agriculture and sheep farming.
In 1846, the Scuola Normale reopened. At the same time, liberal and patriotic ideals were spreading at Athenaeum and a battalion of the university (composed of lecturers and students) distinguished itself in the Battle of Curtatone and Montanara in 1848.
During the Second Restoration in 1851, Leopoldo II united the universities of Pisa and Siena in a unique Etruscan Athenaeum, motivated in part by economic reasons, but primarily for political control. The faculties of theology and law rested at Siena, while those of literature, medicine, mathematics and natural sciences remained at Pisa. Following the Florentine insurrection and the fleeing of the Grand Duke in 1859, one of the initial measures imposed by the provisory government was the restitution to the city of Pisa of its Studium with all six of its faculties.
During the years of fascism, the Pisa Athenaeum was an active centre for political debate and antifascist organisation. After the second world war, the University of Pisa returned to the avant-garde style of learning in many fields of knowledge. To the faculties of engineering and pharmacy, established pre-war, were added economics, foreign languages and literature and politics. In 1967 the Scuola Superiore di Studi Universitari e Perfezionamento S. Anna was founded which, together with La Scuola Normale, formed a prestigious learning and teaching centre.