Built in 1776–78 by the Empress Maria Theresa of Austria (whose country then ruled Milan), it replaced an earlier theatre that had burned. In 1872 it became the property of the city of Milan. The house was closed during World War I. In 1920 the conductor Arturo Toscanini (Toscanini, Arturo) led a council that raised money to reopen it, organizing it as an autonomous corporation. Bombed during World War II, the theatre reopened in 1946, partly through funds raised by benefit concerts given by Toscanini. In late 2001 La Scala closed for extensive renovations. Mario Botta served as the architect of the project, estimated to have cost some $67 million, and the theatre reopened in December 2004 with a performance of Antonio Salieri's Europa riconosciuta, which had been performed at La Scala's opening on August 3, 1778.

La Scala's repertory is more varied than that of the other four or five leading opera houses. It tends to include a large number of unfamiliar works balanced by a limited number of popular favourites. Conductors are given control of casting and rehearsals. The composer Giuseppe Verdi (Verdi, Giuseppe) was closely associated with the house during the 19th century. Toscanini's tenure as artistic director marked one of the finest periods in the theatre's existence.

Associated with the theatre are a ballet company, a ballet school, and a singing school. The expenses of La Scala are met by a combination of ticket sales, a municipal tax, and an Italian governmental subsidy.