According to tradition, in the 16th century, there was a Friday church on the site of the current cathedral. In 1678, a census book mentions the Nikitsky temple at this location. By the end of the 18th century, the church had fallen into disrepair, and a decision was made to build a new temple. In 1773, Oryol merchant Konstantin Semyonovich Pastukhov, who was healed from illness after praying before the miraculous Akhtyrskaya Icon of the Mother of God, decided to build a stone church in her honor at the Friday cemetery. After receiving a blessing, construction began that same year, and in 1775 the church was consecrated.

In 1876, the temple was expanded with the addition of an altar in honor of the great martyr Nikita. The city grew, and the church with its cemetery found itself within the city limits, leading to the cemetery's closure and the church becoming a parish. In 1803, work was done to raise the vaults of the main altar and consecrate a new altar in honor of the Kazan Icon of the Mother of God. In 1823, a tall four-tiered bell tower was built, which was connected to the church in 1870 according to the design of architect I. P. Lutokhin. In 1875, a fence was erected around the church, which was destroyed before the Great Patriotic War. The clergy of the temple consisted of two priests, a deacon, and two psalmists. The parish included 275 households and over 1,000 people. There were two church houses and a candle shop at the market. In October 1897, thanks to church elder M. M. Borzenkov, a church school for forty children was opened, with free education. The first head was priest Vasily Leonov.

After the revolution, the church and its parishioners went through difficult times. During the confiscation of valuables, a silver cross, an ancient shrine of the church, was seized. The Akhtyrskaya church was closed on February 3, 1938, and was used as a grain storage facility. On March 15, 1942, during the occupation of Oryol, the church was reopened and remained so thereafter. During the liberation of Oryol in 1943, one of the first red flags was raised on the church's bell tower.

In 1962, the church was granted the status of a cathedral. In 1986, restoration work was carried out: the walls and ceiling were painted with biblical scenes, the floor was laid with marble, and the iconostasis was decorated with carvings and gilding. The shape of the domes and the spire of the bell tower was restored, and work was done to restore the brickwork. The domes of the church and the spire of the bell tower were covered with copper and gilded.

Among the church's relics are the miraculous Akhtyrskaya Icon of the Mother of God and icons with particles of the relics of the great martyr Nikita and confessor Georgy Kosov. For some time, the relics of St. Tikhon of Zadonsk were housed in the church. In 1991, they were returned to the Zadonsk Monastery, but the hand of the saint remained in the church and is venerated as one of the main relics. An icon was written for it, and a reliquary and shrine were made.

In June 2008, the Smolensk Cathedral was designated as the cathedral of the diocese, but the Akhtyrsk Cathedral was also granted the status of a cathedral.