The scenes of Life of the Mother of God with its miracles and narrative details are depicted in the most poetic cycle – Great Acathistos – on the fourth tier of wall painting. The Acathistos (Greek: "unseated hymn") to the Mother of God was created in Byzantium in the 6th century. The name derives from the fact that during the chanting of the hymn it is expected to remain standing in reverence, without sitting down.

The Acathistos comprises of twenty five verses: thirteen kontakion and twelve oikos.  The first twelve songs of the Acathistos present the main events of the evangelical history, from the Annunciation to the Presentation and illustrated similar to traditional iconographic scenes. They are depicted on the southern wall of the Assumption Cathedral, starting with the first kontakion “Unto the Defender General the dues of victory…”

Siege of Constantinople“Unto the Defender General…” and the AnnunciationKontakion 8

Kontakion 9Oikos 10Oikos 11Kontakion 13

This cycle is continued on the northern part of the western wall and further on the northern wall, describing the second – symbolic and dogmatic half of the Acathistos. The final composition of this cycle is dedicated to the famous thirteenth kontakion illustratingthe veneration of the icon of Our Lady of Vladimir, containing the prayer "O All-Hymned Mother… rescue us all from every calamity, and deliver from future torment…"