Twenty years later, the number of communicants had increased so as to demand the building of another structure of greater proportions. In April of 1859, after several years of negotiations, land was bought from James H. Lucas at Thirteenth and Locust. This was to be the final site for the parish. The chapter asked for designs from four architects: Leopold Eidlitz, New York; John Notman, Philadelphia; Calvin N. Otis, Buffalo; and Richard Upjohn, New York. The guidelines which were given were for a Gothic-style building made of stone, containing galleries, and preferably not including internal pillars. It was asked that the design accommodate 1,000 worshippers in the church and 250 to 280 in the chapel. The cost limitation was set at $75,000 to $100,000.

Designs were submitted by: Otis; Eidlitz and Brown, Brady and Mitchell of St. Louis. The Eidlitz sketches were approved July 11, 1859. Construction began immediately but was slowed drastically by the Civil War. Not only did labor and materials become hard to get but the parish also lost a great deal of financial support from its communicants. The chapter decided to put all efforts into finishing the chapel which was dedicated in 1862. By 1863, Christ Church again began work on the main building. Due to the financial handicap, the plans for the tower, rose window and ornamented porch were dropped. Eidlitz replaced the rose window design with a tripitch window plan. The opening service was held on December 25, 1867. The church was minus the western tower and porch and the flying buttresses. In describing the style, Eugene Rodgers describes it as being: "Fourteenth century Second Pointed or Early English Decorated, and the plan is cruciform. with shallow transepts and apsidal chancel." There were galleries in the north and south transepts and one in the west end which contained the organ. Christ Church became the cathedral for the Diocese of Missouri in June of 1880. The recommendation, and subsequent consecration in 1890, was made by the Right Reverend Daniel Sylvester Tuttle, the current bishop. It was at that time that the church took on its present name: Christ Church Cathedral. But it continued to function as a parish, as well as the diocesan seat.

The cornerstone for the tower was laid in September of 1910 by Bishop Tuttle. Kivas Tully was the architect for the porch and tower, and he reportedly followed Eidlitz´s original designs. Three steel bells were donated by Bertha Drake Scott in memory of her husband, Henry Clarkson Scott. They were cast in steel at the Bochumer Verein Steel Works in Bochum, Westphalia, Germany. They are duplicates of those in the German Pavilion at the 1904 World´s Fair. Bishop Tuttle dedicated the tower, porch and bell in April of 1912.

By 1949, the cathedral building was in bad need of repair. The crumbling sandstone was replaced by limestone. Several of the clerestory windows had been broken, and the series was replaced. A steel structure was added to the beaming of the west wall and tie rods were placed in order to keep the transept walls from buckling. Plans for major renovation and modernization were organized under the Bishop George L. Cadigan in 1960. $250,000 was allocated by the Chapter for work in the cathedral and in the chapel. A Special Planning Committee was chaired by Kurt E. Landberg with Frederick W. Dunn retained as the architect. Gamble Construction was the general contractor. With Dunn as architect, the chapel was totally remodeled between 1960 and 1961 with money given by the Shepley family. The walls were covered with a white tiling, hiding all but a vertical expanse of windows on the south wall. A new organ was installe