Her performance of Violetta in Verdi's La traviata at the Teatro San Benedetto in Venice in 1854 is credited with popularizing the opera after it had initially flopped at its premiere in 1853.

She made her professional opera debut at the Teatro Filarmonico in 1849 in the title role of Vincenzo Bellini's Beatrice di Tenda.

This second production was a complete triumph for both the opera and Spezia Aldighieri, whom Verdi and the critics credited with making the work a success.

In his notes for his unfinished opera Re Lear, Verdi named Spezia Aldighieri as an ideal performer for the role of Cordelia.

In 1861 Spezia-Aldighieri portrayed Abigaille opposite her husband in the title role of Verdi's Nabucco at both La Scala and the Teatro di San Carlo.