Located on Via Salaria, the catacomb is spread over two floors and probably takes its name from a Priscilla of the Acili senatorial family, whose name occurs in one of the inscriptions of the hypogeum of the Acili on the first floor.

Its origin is different from that of the other catacombs as initially the place was an arenarium, then abandoned.

Christians began to use the large and irregular galleries that make up the first floor of the catacomb towards the beginning of the third century, building around twenty niche tombs and digging hundreds of niches in the walls.

In an adjacent area there is the cryptoporticus with the Greek Chapel and a large underground environment, born as a noble family burial ground and then connected to the catacomb.

Among the martyrs buried in Priscilla we remember the brothers Felice and Filippo, who were martyred, probably under Diocletian, together with their mother St. Felicita and the other five brothers Alessandro, Marziale, Vitale, Silano and Gennaro.

Numerous popes were also buried in Priscilla: Marcellino (296-304), Marcello (308-309), Silvestro (314-335), Liberius (352-366), Siricius (384-399), Celestino (422-432) and Vigilius (537-555).

In the hypogeum of the Acili, originally a cistern of water, the inscriptions of the Acili have been found and exhibited. Inside Villa Ada there is the Basilica built by Pope St. Silvestro in correspondence with the tomb of Felice and Filippo. In an area near the basilica a Museum has been set up which collects hundreds of fragments of sarcophagi found during the excavations in the area of the catacomb.