This catacomb is spread out over a large territory which, over the years, spread out across five levels. Presently, only a section of the two upper levels are accessible as well as an area from the middle storey, which also seems to be the oldest area.

Important changes were made to the subterranean network which were, in some way or other, connected to the strong cult that developed around the figure of the martyr Hippolytus. If initially, near the venerated tomb, numerous burials were to be found, these were later destroyed so as to create a larger and more monumental site with the tomb of St Hippolytus placed at its centre. Pope Damasus (366-384) also introduced an inscription written in verse; according to what Aurelius Prudentius says (XI hymn of the Peristephanon),  a painting depicting the martyrdom of the Saint adorned the altar leaning against the tomb.

In the middle of the sixth century, the sanctuary was enlarged and converted it into a true Hypogean basilica, divided into three sections with a large access staircase. The sanctuary was visited at least until the end of the eight century.