Destinn made her debut in Berlin in 1898 as Santuzza in Pietro Mascagni's Cavalleria rusticana. Richard Strauss chose her to create the title role in his opera Salome at its premiere (1906) in Berlin and Paris. She first sang at Covent Garden, London, in 1904 as Donna Anna in W.A. Mozart's Don Giovanni and in 1908 made a triumphant first appearance at the Metropolitan Opera, New York City, as Aida in Giuseppe Verdi's opera of the same name. Other roles in her extensive repertoire included Minnie in Giacomo Puccini's La fanciulla del west (The Girl of the Golden West), Pamina in Mozart's Die Zauberflöte (The Magic Flute), Valentine in Giacomo Meyerbeer's Les Huguenots, and Eva in Richard Wagner's Die Meistersinger.