The ancient origins of this church are attested to by San Gregorio, who tells of a miracle that took place in the VI century that involved a Longobard bishop of Aryan faith who was blinded after an attempt to officiate the church. Other records of its existence date to the X century, when a convent for Benedictine nuns was added. It was first restored in 1234, the year in which the church was consecrated by Pope Gregorio IX. In the XIV century, as a result of constant factional warfare, the monastery was abandoned and rebuilt within the walls of the city at the church of Sant’Agata. In 1771 San Paolo inter vineas underwent extensive interior renovation, but in 1965 another restoration project gave it back its ancient glory.
Today, the church boasts the late-Romanesque shape it received during the renovation of 1234, with a façade not unlike other churches in Spoleto, like San Pietro and San Ponziano, a triple layered entrance and a precious rosette. Inside are three naves delineated by columns topped with Corinthian capitals, while the wide transept is graced with several detached frescoes, components of a noteworthy pictorial cycle dating to the mid-XIII century that decorated the church. The frescoes bear witness to the artistic culture of the Romanesque era, common to southern Umbria and the region of Rome, and whose finest example is the decoration of the Abbazia di San Pietro in Valle outside of Ferentillo.