Catherine's Cathedral, founded on August 30, 1781, is the oldest building on the territory of the former Kherson fortress. It was laid by I. Hannibal, and construction was carried out under the guidance of Moscow architect I.M. Sitnikov from 1781 to 1786. The cathedral was built from pale yellow Ingulec limestone in the style of Russian classicism, featuring a four-column portico on the west facade and a low dome. Six sculptures of saints were placed in the outer niches. The iconostasis, made in the Western European tradition by St. Petersburg masters, has not survived, but some icons are housed in the Kherson Art Museum named after Shovkunenko. The cathedral was consecrated on May 17, 1786.

A year later, it was visited by Empress Catherine II, in honor of whom a prayer service was held. A chair was prepared for her in the 'royal place.' At her direction, an inscription appeared on the pediment of the main facade: 'To the Savior of mankind, dedicated by Catherine II,' which gave the cathedral a second name, the Savior Cathedral.

On November 23, 1791, by the order of Catherine II, the remains of Prince G.A. Potemkin-Tauride, the founder of Kherson and the Black Sea Fleet, were buried in the cathedral's crypt. Around the cathedral rest his contemporaries, buried at his behest. During the Russo-Turkish War of 1787-1791, a memorial was created in the cathedral's enclosure with the graves of fallen heroes.

By 1800, to the west of the cathedral, a stone bell tower was built according to the design of I.E. Starov, which was damaged by an earthquake two years later. In 1806, a temporary wooden bell tower with a large bell, gifted by Catherine II, was erected nearby. It was used until the completion of a new stone bell tower, which has survived to this day.

In May 1922, valuables weighing over 40 kg were confiscated from the cathedral, and in December 1929, the bells were removed and the iconostasis was dismantled, with some icons transferred to the Kherson Local History Museum. In May 1930, an anti-religious museum opened in the cathedral, which was soon closed, and the building was used as a grain storage facility. In August 1941, the cathedral was consecrated again and opened for believers. From the remaining parts of the previous iconostasis, a new one was assembled, and some old icons were returned.

From 1945 to 1947, the Kherson diocese was moved to Catherine's Cathedral from the Assumption Cathedral. After the war, the church operated until 1962, after which it was closed, and church utensils were transferred to the Holy Spirit Cathedral. The building was used for storing firewood and later as a warehouse for the regional book trade. It remained vacant for some time, but in August 1968, the cathedral was designated as a monument of republican significance and began to be used as a tourist site. In the first half of 1969, the sculptures of Apostles Peter and Paul were restored on the cathedral's facade. In 1970, the House of Propaganda of the Kherson Regional Organization of the Society for the Protection of Historical and Cultural Monuments opened in the cathedral, hosting exhibitions, film lectures, and musical evenings.

In the early 1980s, two upper destroyed tiers of the bell tower were restored according to old blueprints, and a gilded cross was installed. However, in 1989, the cathedral building was closed due to its emergency condition.

On August 25, 1991, the church was returned to the Church, restoration work began, and services resumed. In 2007, a new iconostasis was installed in the cathedral.