She was discovered by the impresario Giovanni Zenatello, who took her to New York where she auditioned for Giulio Gatti-Casazza, the general manager of the Metropolitan Opera.The Met desperately needed a star coloratura after the retirement of Amelita Galli-Curci nearly a year earlier. On January 3, 1931, the French woman, unknown in the U.S., made an unheralded Met debut as Lucia in Donizetti's Lucia di Lammermoor. Against all odds, her performance received tremendous acclaim. Pons became a star overnight, and she inherited most of Galli-Curci's important coloratura roles. She also signed a recording contract with RCA Victor Records.
Pons was a principal soprano at the Met for thirty years, appearing 300 times in ten roles from 1931 until 1960. Her most frequent performances were as Lucia (93 performances), Lakmé (50 performances), Gilda in Verdi's Rigoletto (49 performances), and Rosina in Rossini's The Barber of Seville (33 performances). Other roles in her repertoire included Olympia in Offenbach's The Tales of Hoffman, Philine in Ambroise Thomas's Mignon, Amina in Bellini's La Sonnambula, Marie in Donizetti's The Daughter of the Regiment, the Queen in Rimsky-Korsakov's The Golden Cockerel, and the title role in Donizetti's Linda di Chamounix, (a role she sang in the opera's Met premiere on March 1, 1934). In her last performance at the Met, on December 14, 1960, she sang "Caro nome" from Rigoletto as part of a gala performance.
She also made guest appearances at the Opéra Garnier in Paris, Covent Garden in London, La Monnaie in Brussels, Teatro Colón in Buenos Aires, the Chicago Opera and the San Francisco Opera. After her Met farewell, she continued to sing concerts until 1973. Furthermore, she starred in three RKO films: I Dream Too Much (1935) with Henry Fonda, That Girl From Paris (1936) and Hitting a New High (1937).
In 1940, she became a naturalized citizen of the United States. From 1938 to 1958, she was married to the conductor André Kostelanetz. During World War II, she toured the battlefields of North Africa and East Asia. Her country of birth awarded her the Croix de Lorraine and the Légion d'Honneur.
Lily Pons had a small voice, but she demonstrated flawless technique and very secure top notes. With her svelte appearance and good looks, she charmed a public accustomed to buxom sopranos. Nina Morgana, a fellow soprano at the Met, stated that Pons vocalised up to the A-flat above high C (Ab6) without visible effort during their first meeting in early 1930.
George Gershwin was in the process of writing a piece of music dedicated to her when he died in 1937. The incomplete sketch was found among Gershwin's papers after his death and was eventually revived and completed by Michael Tilson Thomas and given the simple title 'For Lily Pons'.
She appeared on the TV show WHAT'S MY LINE? as a celebrity guest in 1955.