The monastery was founded by Elder Ephraim in 1659 at the site where, according to legend, the Isaac icon of the Nativity of the Most Holy Theotokos appeared that same year. After Catherine II's secularization reform in 1764, the monastery was to be closed, but in 1766 it became a non-staff and communal monastery, meaning it did not receive funding from the state. The inhabitants provided for themselves through their own labor, and at that time the monastery was male.

In 1900, the monastery became female. A postal and telegraph station "Semyonovskoye" was located 25 versts away. By 1909, the monastery owned 498 desyatinas and 2326 square fathoms of land, not counting two desyatinas at the mill on the Uhtoma River. Two two-story buildings for the residents were constructed, along with two wooden guesthouses for pilgrims, two clergy houses, a livestock yard, a brick factory, a windmill, and two wooden houses in Poshekhonye. A monastery school operated in the village of Isakovo. The capital of the monastery amounted to 53,536 rubles, while the clergy's capital was 24,775 rubles.

After the 1917 revolution, the monastery was closed and desecrated, with a club and a state farm office established in its main church. By the end of the 20th century, the monastery buildings were abandoned. In 2006, the administration of the Pervomaisky district transferred the monastery to the Yaroslavl diocese of the Russian Orthodox Church for restoration. The monastery now functions as an archbishop's residence. By 2013, a chapel in honor of Seraphim of Sarov was consecrated in the brotherhood building. In 2016, an icon of the Nativity of the Most Holy Theotokos was written for the monastery and delivered by a procession. On February 9, 2019, the day of the transfer of the relics of John Chrysostom, Bishop Benjamin Likhomanov of Rybinsk and Danilov consecrated the bells of the new bell tower.