The construction of the church was initiated by a well-known Petersburg merchant Irodion Chirkin, who also financed the project. The church, resembling the Russian churches of the 17th century, was divided into two floors: the upper one was a so-called "Cold" church, and the lower one - a "Warm" church equipped with a heating system.

The Church is decorated with five bulbous domes. Modern researchers have come to the conclusion that the Church of the Annunciation of the Blessed Virgin is a unique monument of Russian architecture of the 18th century, as its architecture combines the features of pre-Petrine Russian architecture and early Petersburg Baroque. The Church of the Annunciation of the Blessed Virgin is notable for being the largest church in St. Petersburg by the number of thrones (it has seven). The church bell tower is the highest on Vasilievsky island: its height is 42 meters, and the size of the cross crowning the bell tower - 4 meters.

The Church of the Annunciation has long been considered one of the most visited in Saint Petersburg. It also served as a parish church of the Academy of Sciences, and many prominent scientists, including the inventor of the lathe A. Nartov, a geographer and an explorer of Kamchatka S. Krasheninnikov, were buried in the cemetery established next to the church in the 18th century. Among the venerated shrines of the church was a cross containing a particle of the stone of the Holy Sepulchre and 18 particles of the Saints, as well as a cross on the icon of the Annunciation with 6 particles of the Holy relics.

However, these relics disappeared after the October revolution, during the infamous campaign to remove church valuables. In 1935, the Church of the Annunciation was closed. The building was severely damaged by bombing during the Second World War: one of the internal bearing walls cracked. However, after the end of the War, no attempts were made to restore the dilapidated church.

Only in 1992, when the Church was returned to believers the building received the status of an architectural monument of federal importance, and restoration work began.