The church was erected on the site where Narodnaya Volya members assassinated Emperor Alexander II in March 1881.

The church was funded by the Romanov imperial family in honor of Alexander II, and the suffix "on [Spilled] Blood" refers to his assassination.

In order to build a permanent shrine on the exact spot where the assassination took place, it was decided[citation needed] to narrow the canal so that the section of road on which the tsar had been driving could be included within the walls of the church.

An elaborate shrine, in the form of a ciborium, was constructed at the end of the church opposite the altar, on the exact place of Alexander's assassination.

It is embellished with topaz, lazurite and other semi-precious stones,[3] making a striking contrast with the simple cobblestones of the old road, which are exposed in the floor of the shrine.

[2] During the Second World War when many people were starving due to the Siege of Leningrad by Nazi German military forces, the church was used as a temporary morgue for those who died in combat and from starvation and illness.

In 2005, the State Museum of St. Isaac's Cathedral began the recreation of the Holy Gates (permanently lost in the 1920s during the Soviet period).

Orthodox bishop Amvrosij of Gatchina celebrated the consecration of these new Holy Gates on 14 March 2012, the 129th anniversary of Alexander II's assassination.