The first church to stand on the spot where the Epiphany Cathedral is now located was Ss Peter and Paul's Church which was built in 1693 out of wood. Then it was situated just outside the Epiphany Tower of the Irkutsk Kremlin. This church burned down in 1716 and in 1718 work began on replacing it with a stone version. It was only completed in 1746. In 1812 a second bell tower was constructed next to the cathedral.

After the Revolution the church was closed and it was threatened with demolition. It was eventually given protected status in 1960 and then used as a museum. It was returned to the Orthodox Church in 1994. Today it is one of the prettiest churches in Irkutsk both in terms of its external decorations and the new frescoes inside.