In 1508, on the order of Grand Prince Vassily Ivanovich of All Russia, the cathedral built in 1489 was painted frescoes. Feodosy, the son of the renowned painter Dionysius, was trusted to paint the church. Unfortunately, the fire of 1547 destroyed the murals. Restoration works began immediately after the disaster and probably finished by 1551. Later on, the frescoes were renovated several times.

Most huge and significant are illustrations from the Testament, divided into several Cycles—feasts, the Passion, miracles and parables, as well as the Appearance of Christ after the Resurrection.

Another important theme of the murals is the Apocalypse scenes. The events taking place in the sky, the disasters on Earth, the struggle between good and evil and the final victory of justice are related in symbolic language.

Theophanies—appearances of the Godhead—are illustrated in the eastern part of the cathedral, beside the iconostasis. They are alternated on northern and southern walls.

South-west and north-west pillars depict the idea of the inheritance of the Byzantine emperors' power by the rulers of Moscow, as well as the northern perron, northern and western galleries.

A separate group of frescoes are painted on choirs where once side chapels used to be placed.