One of the most ancient churches in Milan, it was commissioned by St. Ambrose in 379–386, in an area where numerous martyrs of the Roman persecutions had been buried.

When St Ambrose arrived in Milan to assume the bishopric, churches in the region were in conflict with each other over the dispute between Arianism and the Nicene Creed as well as numerous local issues.

Ambrose firmly sided with the Nicene partisans, and wanted northern Italy to remain allied to the papacy.

[2] The church building has undergone several restorations and partial reconstructions, assuming the current appearance in the 12th century, when it was rebuilt in the Romanesque style.

The original edifice, like the great churches of Rome of the same epoch, belonged to the basilica type; it consisted of a central nave lighted from the clerestory, two side aisles, an apse, and an atrium.

The latter was used to house the catechumens who attended part of the Mass prior to receiving baptism (this custom disappeared in the early 11th century); the portico, whose entrance has four blind arcades with an open one in the centre, was later used for civil and religious meetings.

The apex of the façade has two orders of loggias: the lower register has three arches of the same span, which join the slightly higher portico ones.

The capitals are decorated by animals (lions, wild boars), and human figures (mostly heads, but also angels and others), as well as by vegetable or fantastic motifs of pre-Romanesque origin.

The ceiling features groin vaults with ogives, each supported by its own semi-pillar or semi-column, which, in the lower section, become a single pillar.

It has nine small columns with decorated capitals and friezes, featuring animal and human figures, as well as vegetable and fantastic motifs.

The front of the ambon is decorated by two gilt copper reliefs, depicting the symbols of two evangelists, Saints Matthew (praying man) and John (eagle).

The apse displays an early 13th-century mosaic, depicting Christ Pantokrator with Sts Gervasus and Protasus, and at the sides, Scenes from the Life of St. Ambrose.

The mosaics on the walls and ceiling were created in the 5th century; these include one of the earliest portraits of St Ambrose.

The crypt, located under the high altar, was built in the 9th century to house the remains of three saints venerated here: Ambrose, Gervasus and Protasus.

The current appearance of the crypt dates from the 18th-century restoration commissioned by cardinal Benedetto Erba Odescalchi and to others from the following century, in which the bodies of the three saints were moved to a silver urn in a space under the ciborium.