According to tradition, the church is named after Praxedes, daughter of the Roman senator Pudens of the second century, a disciple of St Paul. She and her sister, St Pudentiana, were subjected to torture, having been discovered protecting Christians and burying in neighbouring wells the bodies of those martyrs who died during the persecutions of Antoninus Pius. The saint is then said to have died, not directly by martyrdom, but because, appalled as she was by the horror of the persecutions, she begged to die.
Construction of the original church began in the ninth century under Pope Paschal I, and the original structure was then reworked over time, until it took on its present appearance in the nineteenth century.
The site also abundantly recalls the memory of Saints Cyril and Methodius, patron saints of all the Slavs and translators of the Bible into the Slavic tongue, at the behest of Pope Nicholas I, in 867. It was in the monastery of Santa Prassede that they lived, in fact, and, shortly before his death, Cyril, as agreed with his brother, gave the pope the relics of Pope Clement, which they had brought with them to Rome.