An edict issued by the Frankish king of Italy, Lothar I (ruled 818-55) mentions the existence of a higher education institution at Pavia as early as AD 825.This institution, mainly devoted to ecclesiastical and civil law as well as to divinity studies, was then selected as the prime educational centre for northern Italy.
In 1361, the institution was officially established as a studium generale by the Holy Roman emperor Charles IV, who granted the same teaching privileges enjoyed by the University of Paris and Bologna, allowing the institution to teach canon and civil law, philosophy, medicine and liberal arts. It was then expanded and renovated by the duke of Milan, Gian Galeazzo Visconti, becoming the sole university in the Duchy of Milan until the end of the 19th century. Gian Galeazzo worked tirelessly to consolidate the institution and in 1389, he obtained a permission from Pope Boniface IX to teach advanced theology courses.
It was divided into two distinct universities — of jurisprudence (teaching civil and canon law courses) and of arts (teaching medicine, philosophy and liberal arts courses). A rector was elected every year, normally a student who was over twenty years old.The institution offered bachelor, licentiate and doctoral degrees. Despite the politics and hardships due to wars and pestilence, it experienced great growth and the institution was considered to be prestigious as evidenced by the influx of foreign students at the time.In 1412, Filippo Maria Visconti further consolidated the universities, invited prominent scholars to teach there and declared an edict giving serious penalties aimed at preventing students from going elsewhere to study.
Towards the 15th century, prominent teachers such as Baldo degli Ubaldi, Lorenzo Valla, Giasone del Maino taught students in the fields of law, philosophy and literary studies.
During the ongoing Italian War of 1521-6, the authorities in Pavia were forced to close the university in 1524.However, during the 16th century, after the university was re-opened, scholars and scientists such as Andrea Alciato and Gerolamo Cardano taught here. During the Spanish colonization, the research and educational activities of the university stagnated, but there were still prominent scholars such as Gerolamo Saccheri who was still involved with the university.
The rebirth of the university was, in part, due to the initiatives led by Maria Theresa and Joseph II of the House of Austria, in the second half of the 18th century. The initiatives included massive renovations to the teaching programs, research and structure rehabilitations, which were still retained by the university until now.
Throughout its history, the university had benefited from the presence of many distinguished teachers and scientists who wrote celebrated works and made important discoveries — chemist Luigi Valentino Brugnatelli, mathematician Girolamo Cardano (born in Pavia, 1501–76), physicist Alessandro Volta (chair of natural philosophy 1769-1804), poet Ugo Foscolo(chair of eloquence 1809-10), playwright Vincenzo Monti, jurist Gian Domenico Romagnosi, naturalist Lazzaro Spallanzani, mathematician Lorenzo Mascheroni and anatomist Antonio Scarpa.
In 1858, the University was the scene of intense student protests against Austrian rule in northern Italy (through the kingdom of Lombardy-Venetia). The authorities responded by ordering the university's temporary closure. The incidents at Pavia were typical of the wave of nationalist demonstrations all over Italy that immediately preceded the Unification(1859–66). During the 19th century, the medical, natural science and mathematics schools were graced by prominent scientists who propelled the status of the university to new heights. Three Nobel Prize winners taught in Pavia — physician Camillo Golgi (at Pavia from 1861), who was awarded the Nobel Prize in Physiology in 1906 for his studies on the structure of the nervous system, chemist Giulio Natta (at Pavia between 1933 and 1935) and physicist Carlo Rubbia. In addition, distinguished mathematicians Eugenio Beltrami, Felice Casorati and Luigi Berzolari were regular teachers in Pavia. It was also in the University of Pavia, in 1912, Carlo Forlanini discovered the first successful cure for tuberculosis — artificial pneumothorax. In the 1960s, the Faculty of Economics and Commerce as well as Engineering were added to the current lineup of faculties.
During the 20th century, teaching and research activities were carried out by additional prominent scholars such as Pasquale Del Giudice and Arrigo Solmi for law history; Contardo Ferrini and Pietro Bonfante for Roman law; Luigi Cossa and Benvenuto Griziotti for economy, Giacinto Romano for medieval and modern history and Plinio Fraccaro for ancient history.
Also critical to the university's reputation was its distinguished record of public education, epitomized by the establishment of private and public colleges. The oldest colleges, the Collegio Borromeo and Collegio Ghislieri, were built in the 16th century, and in more recent times others were founded through both public and private initiatives — the Collegio Nuovo, the Collegio Santa Caterina and the other eleven colleges managed by EDiSU. In 1997 the IUSS, was established, a Higher Learning Institution (Italian: Istituto Universitario di Studi Superiori) similar to the Scuola Normale Superiore and Istituto Superiore Sant'Anna in Pisa. The IUSS is the federal body that links the colleges of Pavia which constitute the Pavia University System.