The exact date and circumstances of the monastery's founding remain unknown. The monks believe that the monastery was established no later than the 14th century. According to legend, a pious peasant woman found a small icon of Saint Nicholas the Wonderworker by the Shakhma River, previously known as Shartoma, and soon a monastery dedicated to Saint Nicholas was founded nearby. According to another version, the monastery was founded by monks who fled from Suzdal after the Mongol invasion. The first documentary mention of the monastery appears in a spiritual charter from 1425, signed by the archimandrite of the Shartomsky Monastery, Konon. In this document, the princess Maria transfers part of her lands to the Suzdal Spaso-Evfimiev Monastery and the Shartomsky Monastery. The donated lands and the presence of an archimandrite indicate the significant influence of the monastery at that time. In 1506, Grand Duke Vasily III granted the monastery a non-judicial charter, and in 1553, Tsar Ivan IV transferred villages from the possessions of the Gorbaty princes to the monastery, highlighting its growing significance. The 17th century proved less favorable: during the Time of Troubles, the monastery suffered greatly from Polish-Lithuanian raids.

In 1624, the monastery was again attacked by robbers, who killed several monks and stole the treasury. In 1645, under Archimandrite Joasaph, the monastery was completely destroyed by a lightning strike. After the fire, the monastery began to be rebuilt in stone at a new location, closer to the mouth of the Molokhta River. The first stone structure was the Nikolsky Cathedral.

Over time, the monastery lost its significance. The secularization reform of 1764 dealt a blow to its material well-being: significant lands were confiscated, and subordinate monasteries, such as the Shuya Trinity Monastery and others, were closed or converted into parish churches. The monastery became a third-class monastery with 12 monks, managed by igumens. Until the mid-19th century, the Nikolskaya fair was held annually at the monastery's walls, attracting merchants from surrounding regions. In the 18th century, the monastery was supported by the nobility of the Shuya district and merchants from Yaroslavl, Rostov Veliky, Kineshma, and Shuya. In the 19th century, with the advent of the railway, fairs lost their significance, which negatively affected the monastery's well-being. By the end of the 19th century, the monastery was experiencing financial difficulties and repeatedly sought help from the Holy Synod and benefactors. Despite support from Shuya and Ivanovo-Voznesensk manufacturers, after the construction of the Shuya-Ivanovo-Voznesensk railway, which diverted the flow of travelers, the monastery gradually became poorer. In the mid-1920s, the monastery was closed, the cells became residential apartments for residents of the village of Vvedenye, who suffered from a fire, and the church buildings were used as storage for the local collective farm until the early 1980s. In 1960, the Nikolo-Shartomsky Monastery complex was placed under state protection as a monument of cult architecture. In the autumn of 1990, the monastery was returned to the Russian Orthodox Church. By that time, some buildings were already in ruins. Restoration began in the mid-1980s and continues to this day with the participation of the monastic brotherhood.

With more than 100 inhabitants, it is one of the largest male monasteries in Russia. The monastery engages in construction and agricultural work, as well as spiritual and educational activities. Daily services are held according to the monastic rite. In 2012, the diocesan administration of the newly established Shuya Diocese was located here.

Several churches in Ivanovo, Shuya, Yurevets, and the village of Paleh are dependencies of the Nikolo-Shartomsky Monastery. A children's shelter for boys has been established in Ivanovo. Spiritual and educational work is carried out at the dependencies, and non-liturgical discussions are held.