The church is one of the tituli, the first parish churches in Rome. It was known as the Titulus Pudentiana, named after the daughter of the Roman Senator St. Pudens
The church is mentioned in the Liber Pontificalis
, and a tombstone from 384 refers to a man named Leopardus as lector de Pudentiana, this name refers to St Pudentiana
. This latter form is first attested in the 4th century apse mosaic; earlier documents and inscriptions use Pudentiana, who was a daughter of St Pudens and sister of St Praxedes
. The first church or chapel on the site may have been established as early as in the pontificate of Pius I
The first time this interpretation is mentioned in written sources is in a document from 745. The church is built over the house of St Pudens, which after the deaths of Peter and Paul was used as a 'house church'. Archaeologists have dated the first chapel, built in the bath, to c. 140. This fits with the tradition that claims that the first chapel was built by Pope Pius I. It was converted or rebuilt to a regular church after tolerance was granted to Christians in the early 4th century. Dedicatory inscriptions have been preserved, naming «Illiceus, Leopardus and the Presbyter Maximus» as the persons who financed work in the time of Pope Siricius
It was altered in 1588 by Francesco da Volterra, on orders from Enrico Cardinal Caetani
. The dome was added at this time. Some of the changes were very unfortunate, such as the partial mutilation of the mosaics from c. 390.
In 1870, when the façade was rebuilt, remains of Roman houses were found beneath the church and neighbouring buildings. It is possible that one of these houses was the original house-church.