The first church dedicated to the Kazan Icon of the Mother of God was built inside the Tsaritsyn fortress in the early 18th century, but soon, likely, it burned down. In 1709, after the death of priest Peter Dmitriev, another priest, Fyodor Dmitriev, along with parishioners, appealed to the Astrakhan metropolitan Sampson to appoint deacon Alexei Ignatiev as priest.

According to the "Astrakhan Diocesan News" from 1886, the church's income and expenditure book contains records of donations from 1711 and 1720. At the site of the current Kazan Cathedral, there was previously a wooden chapel located near the windmills. Contemporaries noted that the cemetery was not fenced, but it offered a beautiful view of the city.

In 1894, Bishop Nikolai Nalimonov of Saratov and Tsaritsyn inspected the site for a new church, which was laid in 1896 with funds from parishioners. The Kazan Church was built as a cemetery church on Dar Hill and was consecrated on August 23, 1899, by Bishop Ioann Kratir. A significant role in the construction was played by Archpriest Ioann Nikolsky, but the project author is unknown.

From 1902, the church was served by psalmist Nikolai Alekseevich Doletsky, who later became a deacon and was arrested under Soviet power. In 1904, a refectory and bell tower were added to the church. In 1907, Archpriest Ivan Stefanovich Smirnov became the rector of the church, who was elected as a deputy to the diocesan congresses in 1910-1912.

From 1908, priest Alexei Alexandrovich Ushakov served in the church, also performing duties as a district missionary. In 1909, Nikolai Pavlovich Sokolov became a deacon, who was removed from office in 1913. In 1912, the church had 6,306 parishioners, 20 non-Orthodox, 56 Old Believers, and 50 sectarians.

After the October Revolution, most of the church's valuables were confiscated. In 1920, requisition was carried out, and by 1924, the church belonged to the Patriarchal Church. During this time, it was served by Archpriest Viktor Polyakov, Priest Andrei Khmelov, Deacon Proskuryakov, and psalmist Doletsky. The Renovationists filed a complaint against them. In the 1930s, the parish remained active, although it faced persecution. By 1932, it was listed under the "Old Churchmen," but later came under the management of the Renovationists. Documents indicate that the church functioned until the end of 1937. Before his arrest in 1935, priests Vladimir Knyazevsky, Evgeny Megarsky, Efim Sablin, psalmist Fyodor Kochetkov, and deacon Doletsky served here. In 1937, priest Alexander Petrovich Sokolov, deacon Timofey Ivanovich Akimov, and starosta Vasily Ilyich Soloikhov were arrested and sentenced to long prison terms. Before the war, hieromonk Samson served in the church, whose book is kept in the Center for Russian Culture "Resurrection." The church was home to famous fools-for-Christ, such as Blessed Adrian, Tatiana, and Ekaterina. On December 15, 1939, the church was closed and converted into a bread factory.

In April 1946, the building was returned to the believers, and under the guidance of architect V. N. Simbircev, the church was restored. In 1948, it was consecrated by Archbishop Philip Stavitsky. During the reconstruction, efforts were made to preserve the original appearance of the building. In the early 1950s, the church was painted, and in 1954, by order of Patriarch Alexy, it was elevated to the rank of cathedral. In 1955, Sergey Solovyov became the archpriest.

In 2009, the cathedral's key holder, Archpriest Nikolai Picheikin, reported the destruction of the church due to roofing problems. In the spring of 2010, Metropolitan German appealed for help in the reconstruction of the cathedral. The head of the regional administration, Anatoly Brovko, proposed a co-financing scheme for the restoration. One company allocated 15 million rubles for roof repairs. Restoration was carried out both inside and outside. The building regained its pre-revolutionary appearance, the domes were replaced with tents, and four new domes made in Volgodonsk were added. The church continued to operate as usual, and the restoration was completed in 2011.