Traditionally held to be the sister of St. Pudenziana, St. Praxedes joined her in collecting the mortal remains of the martyrs after their sufferings.  It is believed that both her and her sister faced martyrdom as well, although details are scant.  A titulis named after her is recorded in the late fifth century, although this likely existed even earlier.  The titulis was first based in an apartment block in a nearby location.  In the early ninth century, Pope St. Paschal I replaced this with the current church, in order to provide a more fitting place for worship.  Continuing the devotion to the martyrs shown by the patroness of this church, the same pope brought the relics of 2,300 martyrs from the catacombs to be laid to rest here.  In about the year 1080, an altar was built in the crypt.  In a side chapel here is kept a column, said to have been brought here in 1223 from Constantinople during the Latin occupation of that city.  It is traditionally believed to be the column on which the flagellation of Christ took place.  Around the turn of the fourteenth century, structural problems in the church necessitated the construction of three large arches across the nave as means of strengthening the building.  The church was restored under Pope Nicholas IV in the mid-fifteenth century,

St. Charles Borromeo, the cardinal titular here in the late sixteenth century, undertook a great deal of work here.  The great archbishop of Milan not only took care to improve the physical structure of the church, but also to minister to the people of the area, going so far as to invite the poor to eat at his table.  His works to the church structure included blocking off the transept and creating a new area for the choir in its place.  The baroque renovations continued under the next titular, Alessandro Medici, later Pope Leo XI, who also commissioned the frescoes in the nave.  In 1730, a new ciborium and high altar were installed, and the crypt was renovated.  Since then there have been no major changes to the structure, although the façade of the church was restored to its medieval appearance in 1937.