His higher musical education was at Milan Conservatory, where he studied composition and violin. He debuted on the podium at Ferrara in 1898, and was hired by Arturo Toscanini as an assistant conductor at La Scala opera house in Milan.

His career grew through guest conducting at major Italian opera theaters. He debuted in London in 1907 at London's Covent Garden.

In 1909 he was appointed principal conductor at La Scala, serving a term interrupted during World War I (1909-1914, 1917-1918). There he was noted for expanding the repertory away from the standard Italian repertory. He added the Italian works L'Amore dei tre re (1913) and La Nave (1918) by Montemezzi (1913). Foreign operas he introduced in their Italian premieres during this period were Richard Strauss's early opera Feursnot and his masterpiece Der Rosenkavalier, Charles Dukas' Arianne et Barbe-Bleu, Weber's Oberon, and operas by Humperdinck and Rimsky-Korsakov.

He continued introducing new operas while he was on the conducting staff of New York's Metropolitan Opera from 1924 to 1934. He led the first American performances of Puccini's Turandot, Verdi's Simon Boccanegra and operas of Mussorgsky, Falla, and Giordano. He also conducted the world premieres of American operas The Emperor Jones by Louis Gruenberg and Deems Taylors' Peter Ibbetson and The King's Henchmen. During his tenure at the Met he is also credited with helping develop the career of Rosa Ponselle, who became one of the Met's leading stars. He conducted Ponselle in her Covent Garden appearances of 1931 in two operas new to that stage, Verdi's La forza del destino and Romani's Fedra.

In 1934 he returned to Italy, becoming artistic director of Teatro Reale in Rome. He continued his pioneering ways, leading the first Wagner Ring cycle in Italian and the Italian premiere of Berg's Wozzeck. After the War, he resumed leadership at La Scala for the 1946-1947 season, and premiered Britten's Peter Grimes in Italian.

He also was a noted scholar of early Italian opera. His Style, Tradition, and Conventions of Italian Melodrama of the 17th and 18th Century (Milan, 1958-1964) is a major study of its subject. Before him, only a handful of operas of the "bel canto" period and earlier regularly saw the stage, and then in performances bearing the handicap of false tradition. He edited these operas, and brought back operas of Rossini, Bellini, and Donizetti. His talent as a developer of new talent (which the great singer Titto Gobbi said was "infallible") found two great interpreters of this repertory and nurtured them: Maria Callas and Joan Sutherland. He conducted Callas's greatest early performances and recordings, and he led the 1959 Covent Garden production of Lucia di Lammermoor that made the career of young Joan Sutherland.

He was an undemonstrative conductor, using a quiet approach to urge the orchestra, turning stern only when confronting carelessness. He continued his innovative ways, reviving Rossini's Otello in Rome at the age of eighty-four. ~ Joseph Stevenson, Rovi