Framed by slender palm trees, the twin-towered front of St. Mary's Cathedral, with its precise geometry and vertical emphasis, attests to its early date of construction for Texas, where buildings that aspired to architectural monumentality did not begin to be built until the 1850s. The Most Reverend Jean-Marie Odin, the first bishop of Galveston, began construction of St. Mary's just as Pope Pius IX elevated the Galveston-based Vicariate Apostolic of Texas to the rank of diocese in 1847. St. Mary's was cathedral to almost the entire state until additional dioceses began to be created in the 1870s. It is now co-cathedral of the Archdiocese of Galveston-Houston. In 1979 Pope John Paul II designated St. Mary's a minor basilica in recognition of its historical status as the first cathedral in Texas.
The church was designed by American-born, French-trained architect Theodore E. Giraud, according to the research of architectural historian Willard B. Robinson and confirmed by that of Richard Cleary. Giraud was born in Charleston, South Carolina, came with his family to San Antonio in the 1840s (working on occasion with his elder brother François P. Giraud), and settled in New Orleans, where he was the architect of several Catholic churches during the 1850s that share St. Mary's linearity. Beginning in the 1870s, incremental additions and alterations were made to the cathedral by Clayton. Clayton added the square tower that rises from the back of the church in 1878 and added the upper stages and elongated the roof caps of Giraud's twin towers in 1890. These exterior alterations were accompanied by interior alterations. The exposed brick walls were stuccoed in 1922. Otherwise, the church looks substantially as it did in 1890. The major interior alteration, further episodes of embellishment in 1907 and 1922 notwithstanding, was the bleaching of the nave in 1976, which eradicated Clayton's subtle, dark coloration.