The church is supposed to be built on the ruins of the Roman arena where, according to many legends, S. Vitale and S. Agricola were tortured during the Diocletian Empire. Their bodies were identified by S. Ambrogio when he visited Bologna in 392.
The church was rebuilt by the nuns belonging to the Order of St Benedict during the 16th century and still hosts valuable works of art such as the Renaissance chapel by St Maria degli Angeli ascribed to Gasparo Nadi and an evocative crypt belonging to the original building.
The church underwent many changes: it was suppressed and shut down by Napoleon, to be sold and used as a literary circle by the countess Cornelia Barbara Rossi di San Secondo. Only at the end of the napoleonic period, the church was restored to its original use.