The church was built atop of the remains of a 4th-century ancient Roman Thermae, privately owned by the family of Pudentiana, and called Terme di Novato.

Paschal, thus, began two, linked, ambitious programs: the recovery of martyrs' bones from the catacombs of Rome and an almost unprecedented church building campaign.

While on a pilgrimage to Rome with his father around 855-856, the young and future English king Alfred the Great was reportedly deeply impressed and inspired by the church's beauty.

[5] In 1198 the Vallumbrosian monks, an Italian reform movement in the Benedictine Order inspired by Saint John Gualbert, were granted the monastery attached to the basilica by Pope Innocent III and have been present without interruption for more than 800 years since.

Santa Prassede also houses an alleged segment of the pillar or column upon which Jesus was flogged before his crucifixion in Jerusalem (see Flagellation of Christ).

Among these legendary relics retrieved by Helena, which included pieces of the True Cross (now venerated at St. Peter's Basilica[9] with fragments in Santa Croce in Gerusalemme, also in Rome) and wood from the Jesus' crib enshrined at S. Maria Maggiore.

These items, including the Santa Prassede pillar, lack indisputable authenticity, due to absence of forensic evidence and the abundance of other objects claimed during the medieval period to have the same historic function.