Construction of the cathedral was ordered by empress Elizabeth of Russia and occurred from 1743 to 1754, based on a design by architect Mikhail Zemtsov.
The iconostasis and the altar canopy were completed by Kobilinsky woodcutters from Moscow from the drawings of architect Francesco Bartolomeo Rastrelli.
On the holy day of the Transfiguration of Christ (popular name - the Apple Savior), which occurs 6 August (Old Style), the cathedral has traditionally hosted a fruit bazaar.
In 1918 it became a parish church, and the banners, ordnance, and war trophies kept there were removed and transferred to the Artillery Museum; since 1950 those relics have been part of the Hermitage collection.
Stasov directed construction of a fence around the cathedral in 1832-1833 commemorating the victory in the Russo-Turkish War of 1828-1829, the basis of which was the barrels of cannons taken from Turkish fortresses in Izmail, Varna, Tul'chi, Isakchi, and Silistra, and from the battle at Kulevchi.
The engraved coat of arms of the Ottoman Empire is preserved on the barrels and some also bear the names given to the cannons: The Wrath of Allah, Sacred Crescent, Spewing Thunder, I Give Only Death.
In 1916, architect Sergei Osipovich Ovsyannikov planned construction of a burial-vault for the burial of officers fallen in World War I, but the project was never realized.
In a side chapel near the north wall of the church is a hinged icon with depictions of the Transfiguration of Christ, the martyr Pantaleon, and the emperor Saint Constantine.
It was created by the famous Moscow icon-painter Simon Ushakov for Tsar Alexei Mikhailovich and was the favorite icon of Peter the Great and accompanied him at the founding of Saint Petersburg, at the Battle of Poltava, on his deathbed and at his funeral.
It is a copy of a miracle-working icon from the Church of Christ's Transfiguration on Bolshaya Ordynka Street, made in 1711 by the order of the sister of Peter the Great, the tsarevna Natalya Alekseyevna to commemorate the saving of the Russian army during the Prutskiy campaign in the Russo-Turkish War of 1710-1711.