Francesca Sassu was born in the Italian city of Sassari and studied at the conservatory there. She later took part in master classes with Raina Kabaivanska, Renato Bruson, Natale de Carolisnál and Barbara Frittoli.
Over the course of her career, she has performed on many stages all over the world, including Milan's La Scala, the Salzburg Festival, Tokyo's National Theatre, the Opéra Royal de Wallonie in Liège, the Teatro San Carlo in Naples, Venice's Teatro la Fenice, Rome's Teatro dell’Opera, as well as in Turin, Parma, Verona, Bologna, Bari, Spoleto and Cagliari.
She has worked with conductors Paolo Arrivabeni, Daniele Callegari, Alain Guingal, Gianandrea Noseda, Riccardo Muti and Donato Renzetti.
She has been involved in major productions like the modern premiere of Giovanni Paisiello's opera Il Matrimonio inaspettato, in which she portraxed the Countess Olimpia di Sarzana under the baton of Riccardo Muti at the Salzburg Festival. Another modern premiere was Domenico Cimarosa's Cleopatra in Spoleto, where she sang the role of Antonio. She also sang the role of Elektra in Mozart's Idomeneo, with Gianandrea Noseda conducting, at the Le Settimane Musicali di Stresa festival.
Her other roles include Sister Genovieffa (in Puccini's Suor Angelica), Nella (in Puccini's Gianni Schicchi), Leonora (in Verdi's Oberto, Conte di San Bonifacio), Micaëla (in Carmen), Kseniya (in Boris Godunov), Musetta and Mimì (in La bohème), Violetta (in La traviata) and Albina (in Rossini's La donna del lago).
In the 2015/16 season, she portrayed Magda (in Puccini's La rondine) in Pisa and Ravenna, Liù (in Turandot) and Madame Cortese (in Rossini's Il viaggio a Reims) in Novara, the First Lady (in Die Zauberflöte) in Verona, Musetta (in La bohème) in Pavia and Como, as well as Farzana and La Corifea (in Alfredo Casella's La donna serpente) in Turin. She also sang the role of Amelia for the first time (in Simon Boccanegra) in Rovigo.
Her recordings include singing Albina (in La donna del lago) on a record released by Opera Rara, Leonora (in Oberto, Conte di San Bonifacio) in a DVD of a live performance released by Decca, as well as Sister Genovieffa (in Suor Angelica) and Nella (in Gianni Schicchi) in DVDs issued by Rai Trade.