The little church of St. Pudentiana holds some of the earliest memories of the Roman Church within its ancient walls. The Christian history of this site begins with St. Pudens, a Roman senator. He allowed St. Peter to live in his house for at least six years, and it is believed that the first Mass celebrated by St. Peter in Rome took place here. He may also be the Pudens named by St. Paul in one of his letters (2 Tm. 4:21). An early tradition also held that he had two daughters, Pudentiana and Praxedes. These two collected the remains of the martyrs after their death, laying many of them to rest in a well within their home. Another early member of the Roman Church, St. Pastor, is thought to have set up an oratory on this site as well.
Any buildings on this site were either demolished or heavily modified to make way for the construction of a bath hall here in A.D. 139. This structure would have had a large inner hall completely surrounded by an ambulatory. At some later point this building came to be used for Christian worship, with the earliest proof of this dating from 384. At this time the church was known as the Titulus Pudentis, after the traditional patron of Christian worship on the site. A renovation followed, likely in the last decade of the fourth century, which demolished one end of the building and lengthened it. The opposite end was renovated as a sanctuary, being decorated with a mosaic that comes down to us today. Around the year 535, another renovation took place, mainly concerned with strengthening the walls. The church was restored in the late eighth century and again at the turn of the twelfth century. Around the time of this latter date the campanile was built. The interior reached its current state between 1588 and 1599, when a renovation in a restrained baroque style took place. A side chapel, gift of the Caetani family, was created at this time out of a medieval one dedicated to St. Pastor. The apse mosaic was restored several times throughout its history, most recently in 1831; the current façade dates from 1870.