In 1488, Archbishop Joasaph, who was resting in Ferapontovo, invited craftsmen to build the Nativity Cathedral, which was to replace the old wooden church destroyed by a severe fire. This fire damaged many buildings of the monastery; however, a certain "treasure" kept by Joasaph in his cell for the needs of the monastery survived and was likely used for the construction of the stone cathedral. The work lasted about two years, and the features of the masonry and decoration indicate the involvement of Rostov craftsmen. This is logical, considering that Joasaph spent several years in Rostov and was familiar with local architects. In the North, stone churches were rare, and the Ferapontovo Cathedral became the second such structure after the Spaso-Kamenni Monastery Cathedral. Even the Kirillo-Belozersky Monastery built its stone cathedral seven years later. In 1502, the famous painter Dionysius arrived in Ferapontovo with his sons to paint the cathedral. The work began on August 6 and was completed on September 8, in time for the feast day. This unique monument of monumental painting glorified the monastery. Until 1898, the painting remained unknown, and in 1915 it was first restored under the guidance of N. Ya. Epanechnikov. No documentary evidence about the authors of the cathedral has survived, but it is assumed that part of the work belongs to Rostov craftsmen, as confirmed by the similarity with the Assumption Cathedral of the Kirillo-Belozersky Monastery, built by the architect Prokhor of Rostov. This similarity does not diminish the merits of the Nativity Cathedral.

The first service in the Nativity Cathedral in 92 years took place on September 21, 2016, on the feast day, conducted by the rector of the archpastoral residence, Father Alexiy. On June 16, 2018, the Patriarch of Moscow and All Russia Kirill visited the monastery, expressing a desire to revive monastic life in the community. Metropolitan Ignatius of Vologda and Kirillov reported that there is currently no exact information about the revival of the monastery, but even if the monastery becomes active, it will not hinder the work of the Museum of Dionysius Frescoes. On October 15, 2018, the Holy Synod decided to open the monastery in the village of Ferapontovo. The Ferapontovo Monastery is a monument of history and culture of federal significance and has been the only UNESCO World Heritage Site in the Vologda region since 2000.