Construction began around 526 under Bishop Ecclesius, with funding provided in large part by Julianus Argentarius, a banker of Ravenna whose name appears in the dedicatory inscriptions. The basilica was completed twenty years later under Bishop Maximian, by which time Ravenna had passed from Ostrogothic to Byzantine rule. The choice of an octagonal central plan, unusual in the Latin West, follows models from the Eastern Empire — Saints Sergius and Bacchus in Constantinople is the closest comparison — and would in turn become the reference for Charlemagne’s Palatine Chapel at Aachen, built two and a half centuries later.

“The unique character of Ravenna lies in its having combined the traditions of Roman antiquity, the iconography of Christianity, and Oriental and Western styles in a manner unsurpassed in the history of European art.”

ICOMOS evaluation for UNESCO — Ravenna, 1996

The mosaics of the presbytery are the reason most visitors come. On the lower walls, two facing panels show Justinian on the north side, with Bishop Maximian and a guard, and Theodora on the south, with her court of women — both processions presenting offerings, both rendered in the flat hieratic style that would dominate Byzantine sacred art for the next thousand years. The Old Testament cycle on the upper walls treats Abel and Melchizedek, Abraham, and Moses as prefigurations of the Eucharist celebrated below.

San Vitale anchors a circuit of eight monuments inscribed together by UNESCO in 1996 as "Early Christian Monuments of Ravenna". The others — the Mausoleum of Galla Placidia next door, the Arian and Neonian baptisteries, Sant’Apollinare Nuovo, Sant’Apollinare in Classe, the Mausoleum of Theoderic, and the Archiepiscopal Chapel — can all be visited on a single combined ticket. Together they preserve more square metres of fifth- and sixth-century mosaic than anywhere else in the world.