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In the eleventh century there were many jurisconsults at Pisa who lectured on law; prominent among them were Opitone and Sigerdo. There also was preserved a codex of the Pandects, dated, it was said, from Justinian. Four professors of the Law School of Bologna, Bulgarus, Burgundius, Uguccione, and Bandino, successors of Irnerius, were trained here; Burgundius acquired renown by his translation of the Pandects and of Greek works on medicine. Gerardo de Fasiano, Lambertuccio Arminzochi, Zacchia da Volterra, Giovanni Fagioli, Ugo Benci, Baldo da Forli, and Giovanni d'Andrea taught at Pisa in the thirteenth century. In the same century medicine also was taught; the most famous professor was Guido of Pisa, who afterwards went to Bologna (1278). In 1338, as Benedict XII had placed Bologna under interdict, Ranieri da Forli and Bartolo removed to Pisa with a large following. The Studium of Pisa is mentioned in the communal documents of 1340. In 1343 Clement VI erected a studium generale, with all the faculties, including theology; and Charles IV confirmed it in 1355.

The university, however, did not flourish. From 1359 to 1364 it was closed, and was only reopened by Urban VI. Meantime, however, the teaching of law was not discontinued. In 1406 Pisa fell into the power of the Florentines who suppressed the university. In 1473 Lorenzo de' Medici with Sixtus IV's approval closed the University of Florence and reopened Pisa. For its endowment the goods of the Church and clergy were put under contribution to such an extent that Paul III in 1534 recalled the concessions of his predecessors. The most celebrated teachers of this first epoch were the jurisconsults Francesco Tigrini, Baldo degli Ubaldi, Lancellotto Decio, Francesco Alcolti, Baldo Bartolini, Giasone del Maino, Bartolommeo and Mariano Socini; the physicians, Guido da Prato, Ammanati, Ugolino da Montecatini, Alessandro Sermoneta, Albertino da Cremona, Pietro Leoni, and Cristoforo Prati; the Humanists, Bartolommeo da Pratorecchi, Lorenzo Lippi, Andrea Dati, Mariano Tucci; the theologians, Bernardino Cherichini (1478) and Giorgio Benigni Salviati.

In 1543 Cosimo de' Medici undertook to restore the university, and to this end Paul III made large concessions out of the revenues of the Church and monasteries. Several colleges were founded, such as the Ducal College, the Ferdinando, and the Puteano (Pozzi for the Piedmontese). The university at this time became famous especially by its cultivation of the natural sciences. Among its noted scientists were: Cesalpino (botany, medicine, philosophy); Galileo Galilei (mathematics and astronomy); Borelli (mechanics and medicine); Luca Ghini, first director of the botanical gardens (1544); Andrea Vesalio, Realdo Colombo, Gabriele Falloppo; Giovanni Risischi, and Lambeccari in anatomy; Baccio Baldini, Vidio Vidi, Girolamo Mercuriale, Rodrigo Fonseca (seventeenth century), Fil. Cavriami, Marcello Malpighi in medicine. In view of its progressive spirit, Pisa may be called the cradle of modern science. The professors of jurisprudence were rather conservative, but there were not wanting able thinkers, such as the two Torellis, Francesco Vegio, Asinio, Giacomo Mandelli, the two Facchinis, and the Scotsman Dempster; Nicola Bonaparte, who introduced into Pisa the critical-historical study of Roman Law inaugurated by Cujas, Giuseppe Averani, Stefano Fabrucci, historian of the university, Bernardo Tanucci, afterwards minister of Charles III of Naples.

At the beginning of the eighteenth century the university was again in a precarious condition; but the new Lorenzian dynasty sought to strengthen it by increasing the scientific institutes, and revising the statutes; thus after 1744 the rector was no longer elected by the scholars or from their ranks, but had to be one of the professors. In the eighteenth century Valsecchi and Berti won distinction in theology; Andrea Guadegni, Bart. Franc. Pellegrini, Migliorotto Maccioni, Flaminio Dal Borgo, Gian Maria Lampredi, Sandonnini (canonist), the criminalists della Pura and Ranuccia in jurisprudence; Politi, Corsini, Antonioli, Sarti in letters; Guido Grandi, Claudio Fromond, Anton Nicola Branchi, Lorenzo Pignotti, Lorenzo Tilli, and Giorgio Santi in natural science; Angelo Gatti, Antonio Matani, Franc. Torrigiani in medicine; Brogiani and Berlinghieri in anatomy. In 1808 the regulations of the French universities were introduced, but were superseded by others in 1814. The professors were then divided into the faculties of theology, law (comprising philosophy and literature), and medicine. But the number of the chairs increased; in 1840 there were six faculties. In 1847 the "Annali delle Università toscane" were published.

In 1851, for political reasons, the Universities of Pisa and Siena were united, the faculties of jurisprudence and theology located at Siena, and those of philosophy and medicine at Pisa. The former regime was re-established in 1859 with such modifications as the Law of Casati required. In 1873 all chairs of theology were suppressed throughout Italy. Noted professors in law were Lorenzo Quartieri, Federico del Rosso, Valeri, Poggi, Salvagnoli, Franc. Ferrara, P. Emilio Imbriani, and Franc. Carrara (criminalist). Science and letters were represented by the physicist Gerbi; the chemist Piria; the mathematician Betti; the physicians Puccinotti, Pacini, Marcacci, Ranzi (pathology); the criminalist Rosellini, the Latinist Ferrucci; and Francesco de Sanctis, literary critic. Besides the usual faculties, Pisa has schools of engineering, agriculture, veterinary medicine and pharmacy, and a normal high school. In 1910-11 there were 159 instructors and 1160 students.