The church of Saint Prisca stands in the area where, according to tradition, the oldest site of Christian worship on the Aventine hill was situated. This was the "titulus Aquilae et Priscillae", called after the parents of St. Prisca, who was baptized by St. Peter at the age of 13 and is a first-century martyr. The same tradition indicates on this spot traces of the presence of the two great apostles of Rome, Saints Peter and St. Paul.
In the 3rd century, during the pontificate of Pope Eutychian, the body of St. Prisca was found here, and a place of worship was dedicated to her.
According to tradition, St. Prisca was imprisoned for refusing to worship the god Apollo during the reign of Emperor Claudius. Because of her incorruptible faith, she was flogged and then sentenced to death by being thrown to the beasts in the Circus Maximus. By a miracle, however, the lions prostrated themselves and lay down at her feet. Later the saint was condemned to be burnt at the stake, but again, miraculously, the flames left her unharmed. Eventually, to carry out the death sentence, she was taken to the decimo milliario on the Via Ostiense and beheaded.
The domus Priscae is today considered one of the most important Christian sites in Rome. After several renovation projects, one necessitated by the destruction of the complex by Robert Guiscard's Norman invaders in 1084, in 1599 it was rebuilt in the style visitors can view today.