In 218 b.c the Romans founded the cities of Cremona and Piacenza on the banks of the river Po, in the territory occupied by the Cenomani Gauls.

In 148 b.c the roman consul Spurio Postumio started the construction of the road Postumia, running from Genova to Aquileia, that represented a useful means of colonization of the Cisalpine region. Cremona took advantage of this position (along Via Postumia and on the left bank of the Po) becoming one of the major Roman colonies in the Po Valley.

In 69 a .c there was a civil war in Cremona after Nerone's death, three generals fought for imperial power: Otone, Vitellio and Vespasiano, who destroyed the city.

In 603 the Longobards' King Agilulfo obtained the control of the town after a 34 years siege. Cremona grew and the population increased but the town was divided in two: the modern city located near Palazzo Cittanova and the church of Sant'Agata and the old city inside the Roman walls.

In 1098 a big political expansion started in the town with the birth of the "Libero Comune". Cremona became an imperial town ally of Barbarossa and Federico II. Also the economy grew, thanks to the production of fustian cloth exported by means of the Po river.

In 1334 Cremona came under the control of the Duchy of Milan represented by Azzone Visconti.

On October 25, 1441, the marriage between Bianca Visconti, the Duchess of Cremona and Francesco Sforza, Duke of Milan, was celebrated in the church of San Sigismondo. This event brought important changes to the city influenced by the Renaissance.

In 1535 after the death of Francesco II, last heir of the Sforza family, the town was influenced by the Spaniards, testified by the visit of Carlo V in 1541.

In 1567 with the birth of the great composer Claudio Monteverdi, a period of great musical importance started in Cremona. The cremonese violinmaking, already known in Europe thanks to the work of the Amati family, reached its highest levels with the birth of Antonio Stradivari in 1644.

In 1707 Cremona came under the control of Maria Teresa and Giuseppe II of Austria.