As a youth, Spontini studied at the Conservatorio della Pietà de' Turchini in Naples. In 1803, he went to Paris, where he was appointed court composer in 1805.
In 1807, Spontini wrote La Vestale, his best known work. Written with the encouragement of Empress Joséphine, its premiere at the Paris Opera established Spontini as one of the greatest Italian composers of his age. His contemporaries Cherubini and Meyerbeer considered it a masterpiece, and later composers like Berlioz and Wagner admired it. Spontini's later, likewise highly regarded Olimpie (1819, revised 1820, 1826) met with indifference, leading him to leave Paris for Prussia, where he became Kappelmeister and chief conductor at the Berlin Volksopera.
During the 20th century, Spontini's operas were only rarely performed. Perhaps the most famous modern production was the revival of La Vestale with Maria Callas at La Scala at the opening of the 1954 season, to mark the 180th anniversary of the composer's birth. The stage director was famed cinematic director Luchino Visconti. That production was also the La Scala debut of tenor Franco Corelli. Callas recorded the arias "Tu che invoco" and "O Nume tutela" from La Vestale in 1955 (as did Rosa Ponselle in 1926). In 1969, conductor Fernando Previtali revived the opera, with soprano Leyla Gencer and bass-baritone Renato Bruson. (An unofficial recording is in circulation.) In 1995, conductor Riccardo Muti recorded it with a cast of lesser-known singers.
Other revivals of Spontini include Agnes di Hohenstaufen at the Maggio Musicale festival in Florence in 1954, conducted by Vittorio Gui, and in Rome in 1970, with Montserrat Caballé and Antonietta Stella, conducted by Riccardo Muti. Fernando Cortez was revived in 1951, with a young Renata Tebaldi, at the San Carlos (Naples) conducted by Gabriele Santini.