Dating back to pre-Roman times, the town of Pavia (then known as Ticinum Papiae) was a municipality and an important military site under the Roman Empire. Here, in 476, Odoacer defeated Orestes after a long siege. To punish the city for helping the rival, Odoacer destroyed it completely. However, Orestes was able to escape to Piacenza, where Odoacer followed and killed him, deposing his son Romulus Augustus. This was commonly considered the end of the Western Roman Empire.

After the Lombard conquest, Pavia became the capital of their kingdom; but after Charlemagne won the battle of Pavia (773), the city became the capital of his Regnum Italicum, a vassal kingdom of the Holy Roman Empire, until the 12th century.

In the 12th century Pavia acquired the status of a self-governing commune. In the political division between Guelphs and Ghibellines, Pavia was traditionally Ghibelline. In the following centuries Pavia was an important and active town, resisting the domination of Milan, finally yielding to the Visconti family, rulers of Milan in 1359; under the Viscontis Pavia became an intellectual and artistic centre, being the seat from 1361 of the University founded around the nucleus of the old school of law, which attracted students from many countries.

The Battle of Pavia (1525) marks a watershed in the city's fortunes, since by that time, the former cleavage between the supporters of the Pope and those of the Holy Roman Emperor had shifted to one between a French party (allied with the Pope) and a party supporting the Emperor and King of Spain Charles V. Thus during the Bourbon-Habsburg Italian Wars, Pavia was on the Imperial (and Spanish) side.

The defeat and capture of king Francis I of France during the battle gave way to the Spanish occupation which lasted until 1713. Pavia was then ruled by the Austrians until 1796, when it was occupied by the French army under Napoleon. In 1815, it again passed under Austrian administration until the Second War of Independence (1859) and the unification of Italy one year later.