According to tradition, the church was dedicated to St. Mark, patron of Venice, after the help given by that city in the war against Frederick Barbarossa in the 12th century.

However, the first mention of the church dates from 1254 when the Augustinians built a Gothic style edifice with a nave and two aisles re-using pre-existing constructions.

The structure was heavily modified in the Baroque style during the 17th century, when it became the largest church in the city after the Duomo di Milano.

In early 1770, the young Mozart resided in the monastery of San Marco for three months[1] and, on May 22, 1874, the first anniversary of the death of the Milanese poet and novelist Alessandro Manzoni was commemorated in the church by the first performance of Verdi's Requiem, written in his honour.

[2] The façade dates from an 1871 restoration by Carlo Maciachini, who kept the marble portal with tympanum, a gallery of small arches, the rose window and three statues of saints attributed to Giovanni di Balduccio or the Master of Viboldone.