Moffo made her U.S. debut at the Lyric Opera of Chicago in 1957, as Mimi in La bohme; she also sang the role in her San Francisco Opera debut in 1960. But it was at the Metropolitan Opera that she made her name. She made her Met debut in 1959 as Violetta in Verdi's La traviata, a role that she performed with company eighty times, including in her final Met performance in 1976.
John Steane, a Gramophone opera critic, told PlaybillArts that Moffo's voice had "an unusual roundness, generosity, and bloom. Her treatment of roles combined vocal beauty with very credible psychological performances. She approached the psychology of the parts conscientiously and thoughtfully."
During her Met tenure she also sang the title role in Donizetti's Lucia di Lammermoor, Marguerite in Gounod's Faust, and Li‹ in Turandot's Puccini. In Europe, she sang Gilda at Covent Garden, Violetta in Berlin, and other coloratura roles in Hamburg, Vienna, Salzburg, and Milan.
Moffo was born in Wayne, Pennsylvania, to an Italian-American couple in 1932. In high school she played basketball and field hockey. In 1954 she won the Philadelphia Orchestra Young Artists Auditions; she moved to Rome to train as a singer as a Fulbright fellow. She also studied piano, viola, and voice as a scholarship student at the Curtis Institute in Philadelphia.
Moffo also enjoyed a notable recording career, singing Susanna on the 1959 EMI recording of Mozart's Le nozze di Figaro and La traviata with Richard Tucker and Robert Merrill on RCA.
Moffo's career was not limited to the opera stage; she starred in a television production of Madama Buttefly directed by Mario Lanfranchi, a producer for RCA Victor and RAI, whom she married in 1957. They divorced in 1972; two years later she married Robert W. Sarnoff, the chairman of RCA.
With a taxing schedule of opera, TV, and film performances, she was reputed to have pushed her voice too hard and by the late 1960s it had become unreliable. Steane added, "In later years, her voice thickened and her vibrato wasn't as good. Perhaps because she made so many recordings she overtaxed her voice. It seemed to decline suddenly and her singing lost its freshness. She also acquired some unpleasant mannerisms in those later years."
She died of a stroke after battling breast cancer for ten years, according to the Times.