She received international attention at the Glyndebourne Festival, where she appeared as Zerlina in Mozart's Don Giovanni and as Adina in Donizetti's L'elisir d'amore.

[8] Freni resumed her career in 1958 when she performed Mimì in Puccini's La bohème at the Teatro Regio in Turin,[5] and sang in De Nederlandse Opera's 1959–60 season.

Her international breakthrough came at the Glyndebourne Festival, where she appeared in 1960 as Zerlina in Mozart's Don Giovanni,[6] alongside Joan Sutherland as Donna Anna, and in 1962 as Susanna in The Marriage of Figaro, and as Adina in Donizetti's L'elisir d'amore, directed by Franco Zeffirelli.

The voice itself is pure and fresh, operating without seam from bottom to top, marvelously colored at every point by what seems to be an instinctive response to the urging of the text.

From the early 1970s into the 1980s, Freni sang heavier Verdi roles,[7] including Elisabetta in John Dexter's production of Don Carlos, Desdemona in Otello (alongside Jon Vickers), Amelia in Simon Boccanegra, Elvira in the Luca Ronconi staging of Ernani, Leonora in La forza del destino, and the title role of Aida performed in the Houston Grand Opera in 1987.

[7] She never sang Cio-Cio-San on stage, but recorded it twice, not including the 1975 film Madama Butterfly,[16] alongside Plácido Domingo, with Karajan conducting and Jean-Pierre Ponnelle directing.

[2] She played Susanna in the Ponnelle film Le nozze di Figaro, which also featured Dietrich Fischer-Dieskau, Kiri Te Kanawa and Hermann Prey.

After Ghiaurov's death in 2004, Freni continued their work of preserving the bel canto tradition, teaching young singers from around the world.

[17] During this time she sang in Russian operas, such as Tchaikovsky's Tatiana in Eugene Onegin, Lisa in The Queen of Spades, and Ioanna in The Maid of Orleans.

[18] Freni was awarded the Order of Merit of the Italian Republic in the grade of Knight Grand Cross in 1990,[19] and the French Legion of Honour in March 1993.