The Epiphany Monastery was founded in the late 14th century by Grand Duchess Evdokia, the wife of Dmitry Donskoy, who took the monastic name Euphrosinia. The monastery was located in the northwestern part of the Kremlin. On November 20, 1591, Queen Maria Fyodorovna Nagaya, the mother of Tsarevich Dmitry, took the veil here. At that time, the monastery was wooden and had two churches: the Epiphany and the Smolensk.

In 1609, the monastery was burned by the Poles, and the abbess Anastasia and five sisters perished. In 1629, the monastery was restored on its original site with the participation of the nun Martha, the mother of Tsar Mikhail Fyodorovich. The great elder donated money, villages, wastelands, and mills to the monastery.

In 1661, Abbess Pelageya appealed to Tsar Alexei Mikhailovich for permission to relocate the monastery to the vacant lands of the Rostov Archiepiscopal House, and she received approval. By the 1670s, wooden churches in honor of the Epiphany of the Lord and the icon of the Mother of God "Passion" already stood in the new location.

On September 26, 1677, the wooden church of the Epiphany was struck by lightning and burned down. In 1689, Metropolitan Jonah Sysoevich of Rostov issued a decree for the construction of a new stone church. In 1700, local builders erected a five-domed church of the Epiphany of the Lord with a refectory and bell tower, which was demolished in 1834. The main altar was consecrated in honor of the Epiphany of the Lord, and the side altar, in honor of the Smolensk icon of the Mother of God. In the lower church, two more altars were consecrated: in honor of the apostles John the Theologian and Andrew the First-Called, and in 1775, in honor of John the Merciful and Saint Dimitri, Metropolitan of Rostov.

In 1846, the lower altars of the church were abolished, and the premises were occupied by a hospital. In 1853, after the consecration of the new Epiphany Cathedral, the church of the Epiphany was abolished and reconsecrated in honor of the Smolensk icon of the Mother of God. The Smolensk side chapel of the former Epiphany church was rebuilt with the funds of Ivan Arkadyevich Zimin and consecrated in honor of the Exaltation of the Holy Cross. A cross with a relic of more than sixty saints, including Prince Dmitry, was installed there. The interior of the main church was updated, and the walls and vaults were painted with scenes depicting the miracles of the Smolensk Mother of God. The old iconostasis was replaced with a new three-tiered one. A porch was added to the north side of the gallery.

The icon "Annunciation," painted in 1696 by the royal iconographer I.M. Bobylev and gifted to the church by Elder Pachomius, received special veneration.

In memory of the Fyodorov icon of the Mother of God, donated to the monastery by nun Martha, a stone five-domed church of the same name was laid on May 21, 1805, and completed in 1818. From 1822 to 1824, Timofey Medvedev painted the interior of the church, and an iconostasis in the form of a crown was installed. From 1826 to 1837, a porch and bell tower were added, which were dismantled in the 1850s. In 1862, the church was renovated, a new five-tiered iconostasis was installed, and the walls were painted with images of miracles from the Fyodorov icon. The painting work was done by Yegor Dyakonov. In 1890, a bell weighing 500 poods was ordered.

The construction of a new Epiphany Cathedral, designed by K.N. Ton, began on October 19, 1843. In October 1853, three altars were consecrated: in honor of the Epiphany of the Lord, the Tolga icon of the Mother of God, and Saint Nicholas. The cathedral was an exact copy of the Church of Saint Catherine in St. Petersburg. In the 1870s, D.G. Burenin and his son Pavel completed the wall paintings. In 1881, the church was partially renovated, and in 1904-1906, a major renovation was carried out. A chapel was arranged in the lower church under the altar of the Tolga altar for storing the icon "The Unceasing Eye."

In the Epiphany Cathedral, special veneration was given to the copy of the Tolga image, the icon of Saint Nicholas the Wonderworker, and the tomb with relics of John the Merciful.

In 1887, a church in honor of the icon of the Mother of God "It is Truly Meet" was consecrated in one of the towers of the monastery fence, built with the funds of benefactors.

The monastery was closed in the 1930s, and its churches were used as warehouses. In the 1970s and 1980s, restoration was carried out in the Smolensk and Fyodorov churches under the guidance of architect S.E. Novikov. In 1976, the Smolensk church was transferred to the Uglich Historical and Art Museum, and in 1992, the Fyodorov church. In 2000, the Epiphany Cathedral was handed over to the Russian Orthodox Church. In October 2010, the monastery was reopened, and the restoration of the lost shrine began.