Born in Pesaro, Italy, Tebaldi studied music in her hometown and at the Parma Conservatory. She debuted in 1944 as Elena in Boito's Mefistofele. Two years later, she made her first appearance at La Scala, newly reopened after being damaged in World War II, and sang regularly there from 1949 through 1955. She debuted at Covent Garden in 1950 and at the Metropolitan Opera in 1955.

From 1955 until 1973, Tebaldi appeared at the Met in nearly every season, singing Tosca, Desdemona in Otello, Mimi in La bohme, Cio-Cio-San in Madama Butterfly, and Violetta in La Traviata, among other roles. Rudolf Bing, the general manager of the Met, called her "dimples of iron," because of the forceful nature behind her gentle appearance.

Tebaldi was said to have a feud with Maria Callas, already a star at La Scala when Tebaldi began to sing there, but the rivalry, if it existed at all, was felt more on Callas's part. After Tibaldi gave a less-than-successful performance of Violetta in 1950 at La Scala, Callas called her "a poor little thing."

Tebaldi retired from opera in 1973 and from performing entirely in 1976, seeking to avoid, she later said, "the mortifying season of decline."