The Church of the Nativity of the Blessed Virgin Mary served as the winter, warm, cathedral, and refectory church of the Arzamas Spaso-Transfiguration Monastery. The first brief description of the monastery, dated 1585, mentions this church alongside the main church of the Transfiguration of the Lord. Both buildings were wooden, and the church had an altar dedicated to Saint Great Martyr Anastasia. A document from 1626 adds that the church had a refectory annex. The question of when the current stone church was built remains open. An inventory from 1763, compiled by Captain A. Tikhmenev, states that the exact date of construction is unknown. A.S. Petryashin suggests that the church was erected between 1660 and 1690, based on the dates of the consecration of the antimins. If we believe the date on the antimins, the stone church could have existed as early as 1666. At that time, the church altar was consecrated in honor of the Meeting of the Lord, rather than Saint Anastasia, as in the wooden church.

The church premises with the main and side altars were located on the second floor of the massive stone building. A.S. Petryashin hypothesized that the five-domed completion of the church could have been accompanied by three rows of kokoshniks. The original covering of the square base, on which the drums with the domes stood, was four-pitched, and the kokoshniks were included in a high brick attic. Archive photographs from the late 19th and early 20th centuries likely capture this original completion of the church.

The main altar in honor of the Nativity of the Blessed Virgin Mary was consecrated in 1806 by Archbishop Benjamin, in 1830 by Bishop Athanasius, and in 1851 by Bishop Jeremiah. The altar in the Meeting of the Lord chapel was consecrated in 1738 by Archbishop Pitirim and in 1830 by Bishop Athanasius. The replacement of antimins could indicate the completion of construction work in the warm church.

Significant changes to the building's appearance occurred in the 1860s when a single-story annex was added along the southern side, and in 1907 a stone porch was built on the western side. In the 19th century, regular repairs were made to the building, including plastering, whitewashing of the walls, and painting of the roofs.

The Church of the Nativity of the Virgin Mary was used for winter services, so the building was heated. In 1910, there were four Dutch stoves lined with iron on the upper floor, and on the lower floor, four Dutch stoves and one Russian stove located in the brotherhood kitchen. The stove pipes are visible in old photographs of the monastery, but it is difficult to determine which belong to the first or second floor.

The liquidation of the monastery began in 1919 with the arrival of Soviet power. The Church of the Nativity of the Virgin Mary remained the last functioning church and was closed on March 6, 1929, after which it was used as a children's library and residential apartments. In the following years, the upper part of the square base and the altar apses were destroyed, and the eastern part of the second floor was converted into a residential building. By 2012, when the building was transferred to the Church, the porch and covered vestibule on the west were almost completely lost, and the remaining parts were in an emergency state.