The main Orthodox church of Rostov-on-Don is the pre-revolutionary Cathedral of the Nativity of the Blessed Virgin Mary, built in the 19th century. This majestic cathedral adorns the historical center of the city and is one of its symbols. It has survived the Civil War, decades of Soviet atheism, World War II, and remains to this day.

The history of the parish begins in the late 18th century when, after the mass settlement of the sloboda, it was decided to build a church dedicated to the Nativity of the Blessed Virgin Mary. The new church was erected near the current Central Market, then known as the bazaar, and later as the Old Bazaar. The church was laid on February 20, 1781, and consecrated on September 5 of the same year by Archpriest Ioann Andreev. However, on December 27, 1791, the church burned down due to a lightning strike. Thanks to the efforts of the city mayor, merchant Naumov, a decision was made to construct a new stone church with wooden domes. In 1795, the construction was completed, and the church received the status of a merchant church. Another church in honor of the Three Hierarchs was built on its territory.

In 1822, by decree of the Holy Synod, the church was granted cathedral status. It existed in its previous form until the mid-19th century. In 1854, due to the rapid population growth, a project for a new stone church to replace the old one was approved. Construction began in 1854 and was completed in 1860. The church was built according to a standard design by architect Konstantin Ton and externally resembles other projects of his, such as the Cathedral of Christ the Savior in Moscow. Architect Kutepev carried out the direct placement of the church on the site.

The main benefactor of the construction was the church elder Konstantin Mikhailov-Nefedov. Wealthy residents of Rostov-on-Don also participated in the construction. With the funds of I. S. Panchenko, the walls of the cathedral were painted, icons were purchased, a church fence was made, and crosses were installed on the domes.

The five-domed stone church was built in the Russian-Byzantine style and has the shape of a cross. The three-tiered iconostasis is located in the eastern part of the cathedral and is made in the form of a chapel with a tent and a dome. On the cathedral's grounds are a small church in honor of John the Baptist and the baptismal of Saint Nicholas, as well as a bell tower and several service buildings.

In 1875, a bell tower was laid on the western side of the cathedral, designed by architect Anton Campioni with the participation of artist-architect D. V. Lebedev. The construction was financed by Rostov merchants P. R. Maximov, S. N. Koshkin, and philanthropist V. I. Asmolov. The bell tower, 75 meters tall, was completed in 1887 and decorated with elements of classicism and renaissance. The main bell, weighing 16.5 tons, was cast in Moscow with the funds of I. S. Panchenko.

After the Bolsheviks seized the Don in 1920, persecution of the church began. The cathedral was looted, and the buildings were surrounded by a wall. In 1929, the crosses were removed from the domes, and in 1937 the cathedral was closed and handed over to the zoo. Later, the building was used as a warehouse. In 1942, the Soviet authorities planned to blow up the bell tower, but German troops occupied the city and prevented this, preserving part of the bell tower.

In 1942, the cathedral was reopened with the permission of the Germans, and parishioners brought everything necessary for worship. In 1947 and 1949, the abbot Pimen, who would later become the Patriarch of Moscow and all Russia, served in the cathedral. In the late 1940s, restoration work began under the guidance of architect L. F. Eberg. However, the project for restoring the bell tower was rejected, and in 1949 the surviving tier was dismantled. In the 1950s, a narthex was built, and in 1988, the interior decoration was renovated.

In 1999, for the 250th anniversary of Rostov, the bell tower was restored to its original appearance. In 2011, the cathedral was closed for restoration, which lasted until the autumn of 2019. As a result, the frescoes, crosses, and bells were recreated. The cathedral received back its relics, such as the icon of the Don Mother of God and part of the belt of the Blessed Virgin Mary. On October 27, 2019, Patriarch Kirill performed the rite of great consecration and led the Divine Liturgy in the renovated church.

Thus, the main spiritual relic of Rostov-on-Don has once again opened its doors to believers wishing to pray or touch the Don shrine.