Before the war, the Russian community in Berlin used the home church at the Russian Embassy on Unter den Linden. Even then, the rector and head of the Orthodox mission, Archpriest Alexey Maltsev, aimed to build a separate temple.

In 1921, the activities of the Russian Orthodox Church in Berlin resumed, but in 1922, the embassy passed to the Soviet government, and with it, the Orthodox lost their permanent church, being forced to rent temporary premises. Archimandrite Tikhon (Lyashenko), who led the Orthodox Church in Germany, set the goal of returning the church to the community. A construction committee was formed, which managed to gather some donations.

Due to various reasons, the construction of the church was postponed until 1938. The government of Germany, the Evangelical community, public organizations, as well as Grand Duke Cyril Vladimirovich, Tsar Ferdinand of Bulgaria, and the King of Yugoslavia helped in its construction.

The new cathedral was built by architect Shelberg in the Yaroslavl style. The iconostasis for it was taken from an old Russian church in Warsaw. On June 12, 1938, the solemn consecration of the cathedral took place, led by Metropolitan Anastasy (Gribanovsky), the first hierarch of the Russian Orthodox Church Outside Russia.

In 1945, by decision of the rector and the parish, the cathedral came under the jurisdiction of the Russian Orthodox Church of the Moscow Patriarchate, remaining the property of the city. Later, there were many meetings between representatives of the Moscow Patriarchate and the city mayor regarding the transfer of the cathedral to the ownership of the Berlin Diocese, but they ended in refusal.

In 2008, Igumen Daniil (Irbits), responsible for the interaction of the Berlin Diocese of the Russian Orthodox Church of the Moscow Patriarchate with the German government and the public, resumed negotiations with the Berlin city hall about acquiring the cathedral. In 2010, the city authorities agreed to sell the cathedral and the land beneath it to the Berlin Diocese of the Moscow Patriarchate, and the deal was finalized in early 2011.