In 1908 she married the Marchese Luigi Curci, and added his last name to hers. They eventually divorced and in 1921 Galli-Curci married Homer Samuels, her accompanist.
She toured widely in Europe and South America. In 1915 Galli-Curci sang two performances of Lucia di Lammermoor with Enrico Caruso in Buenos Aires. These were to be her only appearances with the legendary tenor. Galli-Curci arrived in the United States in 1916 a virtual unknown. Her stay was intended to be brief, but the acclaim she received for her performance as Gilda in Rigoletto in Chicago, Illinois was so wildly enthusiastic that she accepted an offer to remain with the Chicago Opera Company. She was a member of the company through 1924. Also in 1916, Galli-Curci signed a recording contract with the Victor Talking Machine Company and recorded extensively for the company until 1930. In 1921 Galli-Curci joined the Metropolitan Opera in New York remaining with this organization until her retirement from opera in 1930.
Convinced that opera was a dying art form, Galli-Curci retired from the operatic stage in January 1930 to concentrate instead on concert performances. Throat problems had plagued her for many years and she underwent surgery in 1935 for the removal of a thyroid goiter. Great care was taken during her surgery, which was performed under local anethesia; however, her voice suffered following the surgery. A nerve to her larynx (or "voice box"), the external branch of the superior laryngeal nerve, is thought to have been damaged, resulting in the loss of her ability to sing high pitches. This nerve has since become known as the "nerve of Galli-Curci."
In 2001, Crookes and Recaberen "examined contemporary press reviews after surgery, conducted interviews with colleagues and relatives of the surgeon, and compared the career of Galli-Curci with that of other singers" and found that her vocal decline most likely did not result from a surgical injury.
In 1936, Galli-Curci made her ill-advised return to opera as Mimi in La Boheme in Chicago. It was painfully clear that her singing days were over and after a few more recitals she went into complete retirement living in California until her death in November 1963 at the age of 81. A portrait of Galli-Curci, by the artist Violet Oakley, hangs in the private collection of Bishop Council Nedd II in Harrisburg, PA.