The church is located at the corner of the intersection of K. Marx and Pioneer streets (B. Nikitskaya and Staronikitskaya) in the southeastern part of the city. Its imposing volume dominates the construction on the right bank of the Zusha River. This is one of the best examples of classicism in the Oryol region. Presumably, the Nikitsky parish "higher" than the Zatin (Vyshizatinskaya) sloboda existed as early as the 16th century. The first mention of the wooden Nikitskaya (Myrrh-Bearing) church is found in the census book of Mtsensk from 1625: "The Church of the Holy Myrrh-Bearing Women and St. Nikita the Martyr, wooden, with local icons of God's mercy, books, vestments, bells, and all church furnishings of that same church of priest Gerasim." In 1757, a stone church was built to replace the dilapidated wooden one, but it soon fell into disrepair due to its proximity to the river.

In the early 19th century, with funds from merchant Ivan Nikitich Barykov, the construction of a stone church began at a new location, a block higher than the old one, and was completed in 1818. It had three altars: the main cold altar, the Exaltation of the Holy Cross, in the warm refectory, in the name of the Holy Myrrh-Bearing Women (to the right) and St. Nikita the Great Martyr (to the left). Due to its rich interior decoration and significant capacity, which exceeded that of the old city cathedral, the Church of the Exaltation of the Holy Cross served as a cathedral until the 1840s, when a new cathedral in honor of St. Nicholas the Wonderworker was completed. From January 23 to 25, 1826, the body of Emperor Alexander I was in the church while being transported from Taganrog to St. Petersburg. In memory of this event, members of the royal family gifted the church a chandelier, and a memorial plaque was installed inside the church.

In 1897, the church was last majorly renovated. From 1899, a church school began operating, located in its own wooden house. The church was closed in 1930. During the war, an aerial bomb destroyed the vaults of the refectory. In 1960, the building was placed under state protection, which did not prevent the city authorities from attempting to demolish it under the pretext of dilapidation. Fortunately, the church was preserved.

On February 23, 1973, the spire of the bell tower collapsed. Since 1976, periodic slow restoration work was carried out in the church, which completely ceased by the early 1990s. In 1999, the church was handed over to the Christian community. Initially, restoration work was funded by the parish of the Holy Trinity Church. That same year, regular services resumed in the church. For more than two years, the main altar of the church, which has a fairly large area, was used as a temporary church (a small altar was fenced off in the eastern part, while the rest of the space was occupied by the choir and parishioners). Currently, services are held in the chapel of the Myrrh-Bearing Women.