The first church on the site was built in the 3rd or 5th century, and the baptistery from this church was found during excavations, situated underneath the present Chapel of Relics. A house from the Imperial era was also found, and tradition claims that the church was built over the house in which St Cecilia
lived. In the synod of 499 of Pope Symmachus
, the church is indicated with the Titulus Ceciliae. On 22 November 545, Pope Vigilius
was celebrating the saint in the church, when the emissary of Empress Theodora
, Antemi Scribone, captured him.
The church was rebuilt in 822 by Pope Paschal I
(817-824). At that time, the martyr's remains were brought from the catacombs of St Calixtus
The present church is a result of 18th century rebuilding, performed on orders from the titular of the church, Francesco Cardinal Acquaviva
. Some older elements were preserved. The interior was partly restored in 1822 by Giorgio Cardinal Doria-Pamphilj
, also titular priest of the church.
Improvements were made to the crypt in 1889, and during the work remains of Roman houses from the Republican period were found.
At the present time, the titular of the church is Cardinal Carlo Maria Martini, S.J., Archbishop of Milan. Among the former titulars of the church are Adam Cardinal Easton of Hertford, who is buried here, and Cardinal Wolsey.