According to legend, the Church of Cosmas and Damian was built on the orders of Tsar Ivan the Terrible. In 1552, during the campaign against Kazan, the tsar stopped in Murom and vowed that if the campaign was successful, stone churches would be built in the city over the relics of the Murom saints Princes Konstantin, Mikhail, Fyodor, as well as Peter and Fevronia. Three years later, stone masons arrived in Murom and erected several white-stone churches. On the banks of the Oka, where the royal tent was located from July 10 to 20, 1552, the famous architects Barma and Postnik built the Church of Cosmas and Damian.

According to a land inventory compiled by V. D. Bartenev in 1637, the Church of Cosmas and Damian was "secular," meaning it was built with the funds of the residents of Murom. This inventory mentions that outside the city, on the banks of the Oka, there was a girls' monastery with a stone church in honor of the great miracle workers Cosmas and Damian and a wooden church of Saint Martyr Catherine with an altar dedicated to the Moscow miracle workers: Peter, Alexius, and Jonah. The monastery had 11 local icons, 29 printed and written books, and 4 bells weighing 8 poods. Due to the small number of cells and the absence of an abbess, the monastery fell into decline, and its meadows were owned by Priest Maxim.

The Church of Cosmas and Damian was a cubic single-apsidal church with a multi-faceted tent of complex design, originally standing 12 meters tall. The church was consecrated in 1565.

In 1868, due to soil shifting on the banks of the Oka, the tent of the church collapsed, and the church utensils were transferred to the Church of the Smolensk Icon of the Mother of God. Only in 1901 was a roof installed on the Church of Cosmas and Damian. During the Soviet era, reconstruction projects for the church were proposed, but they were not realized. In 1995, the church was returned to the Russian Orthodox Church.

The tent was restored in a modified form in 2009-2010 according to the project of Vladimir architect V. M. Anisimov. The funds for the reconstruction were provided by the Murom Trinity Monastery.