May 4, 1847 Pope Pius IX made St. Mary's Cathedral, "The Mother Church" of the Catholic Diocese of Galveston-Houston, the cathedral for the newly established Diocese of Galveston. At that time the diocese comprised the entire state.

The original structure, including the central nave, side aisles, transept, and apse, was completed in 1848 and dedicated to the Blessed Virgin. The architect for the Gothic Revival church was Charles G. Bryant. The design, largely inspired by King's College Chapel in Cambridge, England, is in the traditional form of a Latin cross, with the entrance situated to the west and the sanctuary to the east. The structure is 130 feet long and 75 feet wide, with transepts 100 feet wide by 60 feet high. In 1873 a large and beautiful cross with a life size corpus of the Crucified Savior, a gift of John L. arraugh, prominent Galveston business leader and Catholic layman, was laced in the Church. It is now at the right side as you come into the athedral. On the grounds outside the basilica is an obelisk topped with a cross commemorating the yellow fever victims of Galveston in 1853.

A gift of 500,000 bricks from Belgium was used in the construction. In 1876 Galveston architect Nicholas J. Clayton added a transept tower to the roof of the sanctuary. In 1878, a new bell, and a cast-iron statue of "Mary, Star of theSea", was added to the bell tower. Mariners formerly used the lighted crown of the statue as a beacon to guide them into the port of Galveston. During all of Galveston's hurricanes, and particularly the Great Storm of 1900, many a Galvestonian cast desperate and hopeful glances upward at the figure of Mary, "The Protectoress" of the city. In 1884 the Cathedral received another alteration when, under the direction of N.J. Clayton, its two front towers were heightened to bring them into proper proportion with the central tower. Clayton heightened the twin spires at the front of the cathedral to eighty feet and topped them with crosses.

hn Paul II elevated the Cathedral to a "Minor Basilica", an honor bestowed on select churches because of their antiquity or historical importance.