The Catacombs of Domitilla, located on via delle Sette Chiese, is one of the largest cemeteries in underground Rome and originates from some burial grounds set up on land belonging to Flavia Domitilla and donated by this to her freedmen. Flavia Domitilla was the grandson of Flavio Clemente, consul of 95 AD, and related to the imperial family.

As a Christian, Flavia Domitilla was exiled by Domitian to the island of Ponza, where she died.

The catacomb is divided on two main levels. In the so-called Hypogeum of the Flavians, Giovanni Battista de Rossi believed to identify the tombs of the Christian members of the family of Flavia Domitilla, while it is a pagan hypogeum referable between the end of the 2nd and the beginning of the 3rd century, which became Christian and was enlarged mid 3rd century. Towards the end of the third century, the bodies of the martyrs Nereus and Achilleus were placed in a crypt on the second floor which was transformed by Pope Damasus (366-384) into a small basilica, enlarged by Pope Siricius between 390 and 395 until reaching its current size.