The decision to build the cathedral in Astrakhan was made by the City Duma on June 8, 1888, under the chairmanship of V. M. Lazarevsky. The church was planned to be erected in honor of the 900th anniversary of the baptism of Rus as a monument to this event. The sixth area of the city was chosen for construction, where about 11,000 Orthodox Christians lived. A commission consisting of City Duma members selected a site on the banks of the Zaton, in the center of the area, on a wasteland. The location was also chosen due to its position on the border of the Russian and Tatar settlements, allowing the church to perform missionary functions, attracting Tatar Muslims to Orthodoxy and introducing them to Orthodox traditions.

The project by St. Petersburg engineers V. A. Kosiakov and N. E. Ikavitza was recognized as the most suitable on September 10, 1890. Although construction was planned to begin in the year of the 900th anniversary of the baptism of Rus, due to slow fundraising, the poor harvest of 1891, and the cholera epidemic in 1892, work only began in 1895.

Construction actually started on March 5, 1895, when a prayer service was held. The site for the cathedral was reinforced with oak piles, and four months later, the foundation was laid. On June 18, 1895, Bishop Mitrofan Nevsky held a prayer service on the occasion of the foundation laying, during which a commemorative plaque describing the reasons for the construction was placed.

City architect Korzhinsky oversaw the work, which lasted for 7 years. By 1902, the main work was completed, and the commission decided to time the consecration of the church to the 300th anniversary of the Astrakhan diocese.

After the 1917 revolution, the church suffered. In 1919, it found itself in the center of hostilities. In 1923, the Church of St. Vladimir nearly passed to the Renovationists. The rector, Father Ioann Velikanov, began conducting services according to the new style, but the believers did not allow him into the church, and he returned to the Russian Orthodox Church.

In March 1924, Archbishop Faddey Uspensky made the church his cathedral, as other churches were under the control of the Renovationists. The church remained a cathedral until 1936, when it was seized by the Renovationists, and in 1939 it was closed by the authorities and used as a warehouse. In 1967, it was converted into a bus station, painting over all the images of saints.

On January 29, 1998, the head of the Astrakhan region administration, Anatoly Petrovich Guzhvin, ordered the creation of a commission for the reconstruction of the Church of St. Vladimir, with Guzhvin himself as the chairman. On July 27, 1999, the church was returned to the Russian Orthodox Church, and on July 28, 2001, Bishop Ion Karpukhin consecrated the new bells.