The Corpus Christi Cathedral is the second structure to serve as cathedral for the Diocese of Corpus Christi. It replaced Saint Patrick's, the church which had become the cathedral when the city was elevated to Diocesan seat in 1912. After a 1938 fire damaged Saint Patrick's (originally located at 800 Tancahua), the John G. Kenedy family began the drive for donations for a new cathedral by donating this property, the original site of their family residence, to the diocese. Bishops E. B. Ledvina and Mariano S. Garriaga retained architect C. L. Monnot of Oklahoma, who designed this lofty, two-story structure.

A stylized interpretation of the architecture of the early spanish missions, the cathedral features asymmetrical bell towers with painted terra cotta domes, art glass windows, and a low-pitched gable tile roof. The cornerstone was laid March 1, 1940. Pope Pius XII advised Bishop Ledvina to name the new structure after its host city, whose name in latin means "Body of Christ". Later that year on July 17, 1940, the new structure was dedicated as the Corpus Christi Cathedral.