According to the scribal books of Kazan and the Kazan district, in 1565, on the site of the modern Nikolski Cathedral, there was a wooden church of St. Nicholas the Wonderworker, known as the "Church of Nikola Borovsky."

By the end of the 17th century, a stone temple without columns, with one dome, known as the Nikolo-Nizskaya church, was built in its place. It had two altars: one in honor of the Nativity of Christ and the other, in the name of John the Warrior, located in the bell tower.

Around the same time, a summer Pokrovskaya church could have been built, representing a stone six-column three-apsidal temple. The dates of its origin vary: the antimension indicates 1696, while the clerical records point to 1703. These dates may refer to either the renovation or the construction of the temple.

In the 1720s and 1730s, a five-tier bell tower was erected near the Pokrovskaya church.

In 1834 and 1871, the Nikolo-Nizskaya church was served by priest Mikhail Pavlovich Poletayev, the son of the previous priest and a graduate of the Kazan Theological Seminary. During his service in 1857 and 1862, a two-story stone house for the clergy was built.

The construction and renovations of the temple were financed by parishioners, although the congregation was small and consisted mainly of low-income individuals. Thanks to the efforts of priest Nikolai Maksimovich Varushkin, who served from 1871 to 1903, it was possible to attract benefactors for the renewal of the temple. The main funds were provided by merchants Pavel Vasilyevich Shchetinkin, Vasily Ivanovich Zausailov, Alexander Nikiforovich Sveshnikov, and Grigory Nikolaevich Gorinov. Their names are immortalized on the memorial plaque of the temple. Of them, only G. N. Gorinov was a parishioner and the elder of the church.

In 1883, the old Nikolo-Nizskaya church was dismantled, and in 1885, a new building in eclectic style with elements of classicism was constructed.

In 1892, the cold Pokrovskaya church was renovated, which, after partial reconstruction, became five-domed.

In 1930, due to anti-religious policies, the Nikolo-Nizskaya church was closed. By the time of the revival of the Kazan diocese in 1942, only the cemetery church of the Yaroslavl Wonderworkers was operating in Kazan.

Under Archbishop Germogen Kozhin, in October 1946, the second Orthodox community was registered in Kazan, to which the Nikolo-Nizskaya and Pokrovskaya churches were transferred. They were granted the status of the Nikolski Cathedral, and the attached altar of the cathedral for early liturgies was consecrated in honor of the 40 martyrs of Sebaste.