She was born as Amelita Galli into an upper-middle-class family in Milan, where she studied piano in her youth. She was inspired to sing by her grandmother. By her own choice, Galli-Curci's singing was largely self-trained, from listening to other sopranos, reading old singing method books, and practicing piano exercisises with her voice.
She debuted in the role of Gilda in Rigoletto in 1906. She quickly achieved fame.
In 1908 she married the Marchése Luigi Curci, and added his last name to hers.
She toured widely in Europe and South America. A 1916 visit to the United States was intended to be brief, but the reception to her performances of Rigoletto in Chicago, Illinois were so wildly enthusiastic that she accepted an offer to star with the Chicago Opera Company. She stayed with the company through 1924, in which year she moved to the Metropolitan Opera in New York City.
She recorded extensively for the Victor Talking Machine Company.
She retired in 1930, due to throat problems. In 1935 she had throat surgery, then returned to the stage to give a series of recitals, but her voice was no longer what it had been and she returned to retirement in 1937.
She spent her retirement in La Jolla, California where she died at the age of 81.