If we could have stood in front of this church two millennia ago looking out on the Via del Corso, a parade of history would have passed before us: not only Caesar coming into the city after crossing the Rubicon and Constantine after his victory as Milvian Bridge, but also a continuous stream of ordinary folk, among whom may well have been the great Apostle to the Gentiles, St. Paul.  Tradition holds that he stayed here for part of his time in Rome.  Archeologists have found remains dating back to the first century A.D. beneath the church, possibly being part of the actual house in which St. Paul stayed.  In the third century, a large outdoor portico with several small shops was built on this site, running from here up as far as Piazza Venezia.  At some point after the fall of the Western Roman Empire, some of this structure was converted into a diaconia, part of which was a small oratory.  This transformation happened possibly as early as the late fifth or sixth century.  Some rooms from this oratory remain underneath the present church, and in these are fragments of frescoes depicting various Christian scenes, including some of the imprisonment of St. Paul.  Some centuries later the diaconia was replaced by a church, consecrated in 1049.  This church had the opposite orientation as the current one, with the sanctuary being closer to the Via del Corso, also known as the Via Lata or “wide street” because this was one of the largest streets in the city at the time.  Around this time, this church became used for the stational Mass of today, as the assigned station, St. Cyricaus, had by then fallen into ruin.

At the end of the fifteenth century, this church was in turn replaced with the current one, with demolition beginning in 1491 and the new church, with the orientation changed so that it faced the Via del Corso, being dedicated in 1506.  At this time the Triumphal Arch of Diocletian was also demolished, which once stood near the current location of the front doors of the church.  The present church owes most of its appearance to the mid-seventeenth century.  Beginning in 1636 and continuing over the next 15 years, the interior was renovated, beginning with the apse and sanctuary and continuing with the nave.  The current façade, complementing the surrounding palace of the Doria-Pamphilij family, was built between 1658 and 1662, with the lower church, including some of the remains of the old diaconia, being restored at the same time.  Decoration continued into the early eighteenth century, giving us the current appearance.