In 1928, Archbishop Simon (Vinogradov) of Shanghai appealed to Russian Orthodox believers in Shanghai to raise funds for the construction of a large Orthodox church. The cathedral was laid in May 1933 thanks to the efforts of Metropolitan Victor (Svyatin). The church project was created by artist Y. L. Likhosonov, and the technical work was carried out by engineers B. F. Zenzinov and N. A. Belanovsky. Construction was completed in 1937 under the guidance of Bishop John (Maximovich) of Shanghai.

The church reached a height of 35 meters and accommodated about 2,500 people, including 300 in the choir. The total cost of construction and equipment was over 150 thousand dollars. During the Cultural Revolution, the cathedral was closed for services.

In 2002, the Russian community of Shanghai protested against the leasing of the cathedral building, fearing that its interior would be altered and that the cathedral would turn into a nightclub. They expressed regret over such developments. The Russian Club of Shanghai has since continued to seek the return of the cathedral.

On May 15, 2013, during the first visit of the head of the Russian Orthodox Church to China, Patriarch Kirill of Moscow and All Russia held a divine liturgy in the building of the former cathedral.

In May 2014, as part of President V. V. Putin's visit to the PRC, a photo exhibition titled 'Russians in Shanghai. 1930s' was held in the cathedral. The use of the building for humanitarian projects related to the Russian presence in Shanghai is part of the efforts of Russia and the Russian Orthodox Church to preserve monuments of Russian spiritual heritage in China and support the Chinese Autonomous Orthodox Church.

On April 28, 2019, an Easter service was held in the cathedral, attended by several hundred believers. This was a one-time event permitted by local authorities.