The museum originates from the collections of Marquis Giuseppe Sigismondo Ala Ponzone. The collection includes several sections. The first is dedicated to the Middle Ages and the Fifteenth Century, with sculptures, detached frescoes, ceiling panels, and a wide selection of works related to the Bembo family. It is followed by Cremonese painting of the Sixteenth Century, offering a complete anthology of painters documenting the transition from the fifteenth-century tradition to the modern style and the affirmation of the new Renaissance sensibility through the works of Camillo Boccaccino, Gian Francesco Bembo, and the Campi family, precursors of the naturalistic sensibility that will lead to Caravaggio, illustrated here by the famous Saint Francis in Meditation.

The San Domenico Hall houses a series of works from the demolished church of the Dominican friars and showcases Milanese contributions to the local culture of the seventeenth century (Cerano, Nuvolone, Procaccini). The following rooms are dedicated to Cremonese still life, portraits of the Ponzone family, and evidence of painting from the seventeenth (Genovesino), eighteenth, and nineteenth centuries with the affirmation of Neoclassicism (Diotti) and Romanticism (Piccio).

The last rooms host a selection of applied arts (oriental porcelain, Lombard and European ceramics and majolica, ivories, enamels); the section dedicated to the iconography of Cremona, with works related to the city's history and its pictorial representation; an overview of Lombard and Cremonese painting from the late eighteenth and nineteenth centuries.

Rooms for Music are one of the spaces of the Museo Civico Ala Ponzone dedicated to string instruments, see if you can find them: This collection gathers instruments that belonged to renowned collectors, musicians, and aristocrats. In addition to interesting examples of violins, violas, violas d'amore, pochettes, and ghironde, there are around fifty plucked string instruments including guitars, English guitars, mandolins, and lutes, built by the main European craftsmen active in the seventeenth, eighteenth, and nineteenth centuries.