During the visits of Emperor Alexander II to Kissingen in 1864 and 1868, the need for a Russian church in the city was discussed. However, it was only thanks to the efforts of Archpriest Alexei Maltsev and the Holy Prince Vladimir Brotherhood that in 1897 fundraising began, a building committee was formed under the chairmanship of the Russian envoy to the Bavarian court A.P. Izvolsky, and a plot of land was acquired. The famous St. Petersburg architect Viktor Alexandrovich Shreter developed the church plan for free, which, unlike other Russian churches in Germany, was executed in the Byzantine style, similar to the St. Vladimir Cathedral in Kyiv. The frescoes of the church, created by artists Dmitry Kiplik, Alexander Blaznov, and Ivan Popov in 1905, also followed the example of the frescoes of the Kyiv cathedral by Viktor Vasnetsov.

The laying of the church on the day of the Kazan Icon of the Mother of God on July 8/20, 1898, and its consecration on the day of St. Sergius of Radonezh on July 5/18, 1901, were conducted by the head of the Romanian Church, Metropolitan Joseph Georgyan, and the rector of the Russian embassy church in Berlin, Archpriest A. Maltsev. The church was built in memory of the coronation of Emperor Nicholas II in 1896, although he never visited it. Nevertheless, other members of the Imperial House prayed in the church: Grand Duke Pavel Alexandrovich with his wife Princess Paley and son Prince Vladimir Paley (1903-1911), Grand Duke Georgy Mikhailovich (1910-1913), Grand Duke Mikhail Alexandrovich with his wife (1913), Grand Duke Mikhail Mikhailovich (1909), Grand Duchess Ksenia Alexandrovna with her husband Grand Duke Alexander Mikhailovich (1910), Grand Duke Boris Vladimirovich (1933-1934), Grand Duchess Kira Kirillovna (1945), and Princess Vera Konstantinovna, who led the Holy Prince Vladimir Brotherhood for a long time (1951). During World War I, the church was closed and was under sequestration. In June 1921, Archbishop Evlogy (Georgievsky) held a service in the church, resuming worship. In 1944-45, the church house became a refuge for Russian refugees, mainly priests with their families. The then rector of the church, Archpriest Alexander Bogachev, who himself survived captivity and imprisonment in Gestapo prisons, provided significant assistance to the refugees. Since the mid-1990s, a fairly large parish has formed at the church, consisting mainly of settlers. Since 2005, the church has been served by Priest Valery Mikheev from Landshut. Since 1938, the church has been part of the German Diocese of the Russian Orthodox Church Outside Russia (ROCOR).