The monastery was located on the left bank of the Volga, 3 km above Uglich, in the area of the modern village of Pokrovskie Gorki. Its foundation dates back to the mid-15th century. In the late 1460s, Paisius Uglichsky became the abbot. By the end of the 15th century, the monastery received land grants from Andrei the Great in the vicinity of the city. With the funds from the Uglich prince, a cathedral was built in 1482 in honor of the Protection of the Mother of God. The monastery was a significant cultural center of the region, where artels of icon painters worked and workshops for the production of icons and handwritten books existed.

From the early 16th century, after the death of the venerable Paisius and the acquisition of the miraculous icon of the Protection of the Mother of God, the monastery became a spiritual center and a place of pilgrimage. In 1509, by the decree of Prince Dmitry Zhilka, the monastery was granted the village of Arkhangelsk with its hamlets. In 1534, Ivan IV and in 1585, Tsarevich Dmitry provided the monastery with significant privileges. By the end of the 16th century, the monastery owned a settlement on the city side and 36 villages with hamlets. During this time, a stone church of the Epiphany of the Lord, a church of Nicholas the Wonderworker, and a wooden church of Sergius the Wonderworker were built on its territory. In 1609, the monastery was ravaged by the Poles, and Abbot Anthony and 40 monks perished. Restoration began around 1619.

In the late 17th century, the cathedral church on the monastery grounds was rebuilt, a new stone Epiphany church with a refectory was erected, a bell tower was constructed, and the building of a fence with towers was started. In 1692, by the decree of Patriarch Adrian, an archimandrite was established in the monastery, with the first archimandrite being the cross-bearing hieromonk of the patriarch, Elder Macarius. The archimandrite was abolished in 1764. Between 1828 and 1831, a 30 m high bell tower was built in the monastery, from 1840 to 1842 the chapel of Dmitry of Rostov was rebuilt, and in 1860 a new guesthouse was erected. The monastery also housed residential and economic premises, as well as a two-class primary school. Here were buried the venerable Paisius, Fyodor, Danila, and Alexey Adashev, local church figures.

The monastery was abolished in the 1920s. In 1935, a decision was made to create the Uglich Reservoir, which led to the flooding of the territory where the monastery was located. That same year, construction began on the Uglich hydroelectric station and navigation lock, as well as the preparation of the reservoir area, including mass deforestation and demolition of buildings. The main work was carried out by prisoners of Volgolog, among whom were representatives of the intelligentsia, clergy, and peasantry. Bricks from the destroyed monastery buildings were used in the construction of the hydroelectric station and lock due to their high quality.

In 1939, the filling of the Uglich Reservoir began, and soon the waters engulfed the site where the monastery in honor of the Protection of the Most Holy Theotokos stood. This place, where many Russian saints worked and prayed, is now hidden underwater. The monastery could have been saved by embanking the area or changing the location of the hydroelectric station construction, but the Volga cascade of reservoirs was created to destroy the Russian spiritual heritage, and the generation of electricity was merely a pretext.

In 1997, a commemorative cross was erected on the shore of the reservoir in the village of Pokrovskie Gorki in memory of the monastery. Every year in late autumn, when the water level in the reservoir decreases, three small islands appear on the surface, symbolizing the memory of the three saints: Paisius, Adrian, and Anthony.