During the opera’s earliest days, the productions were limited to the Neapolitan opera buffa (comic opera), a genre popularised by 18th-century composers Giovanni Paisiello and Domenico Cimarosa. Later, the house rejuvenated its repertoire with pieces by Ferdinando Paer and Giovanni Simone Mayr, displaying an increased interest in the French operatic tradition. Thus, La Scala slowly began to appreciate a new operatic genre: the Romantic opera of Gioachino Rossini. Following the rise of Rossini, the Teatro alla Scala became the main venue where his Italian serious operas (opera seria) were staged, among others such as ‘Il Turco in Italia’, ‘La Cenerentola’, ‘Il Barbiere di Siviglia’, ‘La Donna del Lago’, ‘Otello’, ‘Tancredi’ and ‘Semiramide’. In 1816, La Scala also staged Mozart’s ‘Die Zauberflöte’. The next era of glamourous primas (first performances, premieres) came with the period 1822-25, when the theatre saw the productions of ‘Chiara e Serafina’ by Gaetano Donizetti, ‘Il Pirata’ by Vincenzo Bellini, followed by a long line of successful Donizetti performances, such as those of ‘Anna Bolena’, ‘Lucrezia Borgia’, ‘La Favorita’, ‘Linda di Chamonix’ or ‘Don Pasquale’. The Bellini operas staged in this opera house until the early 1840s included ‘I Capuleti e I Montecchi’, ‘La Sonnambula’, ‘Beatrice di Tenda’ and ‘I Puritani’.

The year 1839 was of particular importance for the opera, as it marked the beginning of an entire Verdi era at La Scala. The first opera of the long Verdi cycle was ‘Oberto Conte di San Bonifacio’, followed by the disappointing ‘Un giorno di regno’ and the highly successful ‘Nabucco’, which was performed in 1842. ‘Nabucco’ was the first triumph of Verdi and it paved the way for more stagings of his works at La Scala. However, following the performances of his ‘I Lombardi alla Prima Crociata’ and ‘Giovanna d'Arco’, Verdi's collaboration with La Scala ceased in 1848. In 1869, Verdi renewed his connection with the Milan opera, initiating it with the re-staging of his ‘La Forza del Destino’. The year 1872 saw the first performance of ‘Aida’ and in1874, the first rendition of ‘Requiem’ took place on the prestigious La Scala stage.

The next important period in the history of the opera came when Arturo Toscanini became the new artistic director of the theatre. Toscanini, considered one of the greatest conductors of all time, initiated a tradition of new interpretations of Verdi’s classical pieces, and became famous for his productions of works by Richard Wagner and Giacomo Puccini, including ‘Le Villi’, ‘Manon Lescaut’, ‘Madame Butterfly’, ‘La Fanciulla del West’, as well as the glamorous 1926 premiere of ‘Turandot’. The late 19th Century was marked by the works of Mascagni, represented by ‘Iris’, ‘Parisina’, ‘Le Maschere’, pieces by Ruggero Leoncavallo, Francesco Cilea and Umberto Giordano, as well as some foreign composers such as Richard Strauss, Igor Stravinsky, Claude Debussy and Ippolito Pizzetti. Between the two World Wars, the world's best performers sang at La Scala. Following a severe bombing in 1943, La Scala reopened just three years later, hosting conductor Herbert von Karajan, and singers Maria Callas and Giuseppe Di Stefano.

During the second half of the 20th Century, La Scala concentrated on a more contemporary repertoire, and under director Francesco Siciliani, performed pieces by Sergei Prokofiev, Benjamin Britten, George Gershwin, Francis Poulenc, Arnold Schoenberg, Dmitry Shostakovich and Paul Hindemith. This era was also marked by conductors Luciano Berio, Bruno Maderna, Giacomo Manzoni, Claudio Abbado and Ricardo Mutti. La Scala staged the works of composer Franco Donatoni and Roland Petit, as well as new interpretations of Rossini’s classical repertoire.