In 1747 José de Escandón commissioned an expedition to map the area south of the Presidio of La Bahía. Don Joaquín Orobio Y Basterra with 25 men and one priest reached the mouth of the Nueces River and named the bay he found San Miguel Arcángel. In 1766 the mission and Presidio of La Bahía was moved for the fourth time to its present location in Goliad. It was from here, responding to rumors that the "English" had landed somewhere south and east along the coast, Don Diego Ortiz Parrilla lead an expedition to the Gulf. Although he found no "English" he did re-map the area and re-named the bay Corpus Christi. The named stayed and remains significant for South Texas Catholics, who live in the only diocese in the world named after the Body of Christ.

Historically, the Catholic Church, in the form of religious missionaries, played a large role in the development and growth of early South Texas. People of faith from the pioneer era to the present day have answered callings and shaped the face of the South Texas Church.

Church administration during the early years was varied. At times, South Texas was administered under the Dioceses of Guadalajara, Monterrey and Durango of Mexico. Political situations made it necessary to change the administration of the Church, and in 1841, the entire Republic of Texas was made a Vicariate Apostolic.

Bishop Jean Marie Odin was named the first prefect apostolic in 1842, and he went to live in Galveston. Operating under the Diocese of Galveston, the Church flourished and grew, providing South Texas with a steady increase in the number of Catholics. He later held the title of Bishop of Galveston and had jurisdiction over all of Texas, and with only four priests to serve the entire area, he quickly made recruitment of men and women religious a major part of his administration.

In 1874, the Diocese of Galveston was divided into the Diocese of San Antonio and the Vicariate Apostolic of Brownsville. Bishop Dominic Manucy was named the first Vicar Apostolic of Brownsville, and in 1875, he moved his residence to Corpus Christi. He died in 1885.

Through the years, missionaries traveled on horseback, visiting as many ranches and settlements as they could reach. It was not unusual for bishops to travel in this fashion, taking as long as two years to cover South Texas on their confirmation tours. In fact, Bishop Peter Verdaguer, who succeeded Bishop Manucy in 1890, died while on a confirmation tour of rural parishes in 1911.

In 1912, the vicariate was raised to the rank of the diocese, with Corpus Christi designated as the Diocesan See. A tiny adobe and shell building, the first St. Patrick's Church which was built by Father Bernard O'Reilly in 1853, had been replaced in 1881, when Bishop Manucy undertook the building of a new church. This new St. Patrick's Church was elevated to a Cathedral.

Bishop Verdaguer was succeeded by Bishops Paul Joseph Nussbaum (1913-1920), Emmanuel Ledvina (1921-1949), and Mariano Garriga (1949-1965). It was under Bishop Thomas J. Drury (1965-1983) that the four southern counties of the Diocese of Corpus Christi were separated and became the Diocese of Brownsville. In May 1982, the Diocese of Victoria was established.

Bishop Rene H. Gracida next served as the Shepherd of the Diocese from July 11, 1983 through April 1, 1997. During his time as ordinary of the diocese, Bishop Gracida issued a decree of erection of the Western Vicariate of the Diocese of Corpus Christi. The decree states that the vicariate was created to promote the pastoral good and unity of all the people of God in this area, "especially in the view of the possible erection of a new diocese in that region in the not so distant future." The Western Vicariate encompasses the counties of Webb, Zapata, Jim Hogg, and the southern portion of La Salle County.

On June 26, 1995, Bishop Roberto O. González, was officially welcomed to the diocese as the coadjutor bishop. He became the sixth Bishop of the Diocese of Corpus Christi on April 1, 1997.

During his time as shepherd of the diocese, Bishop Roberto worked toward consolidating the diocesan infrastructure and uniting the faithful throughout the diocese. He stressed that the present era is one of hope as the universal and local Church prepares for the anniversary of the Incarnation of Jesus Christ in the Great Jubilee Year 2000. He became Apostolic Administrator of the Diocese of Corpus Christi and Archbishop of San Juan de Puerto Rico on May 8, 1999.

On March 17, 2000, Bishop Edmond Carmody was installed as the seventh Bishop of the Diocese of Corpus Christi.

On March 25, 2010, Bishop Wm. Michael Mulvey was installed as the eighth Bishop of the Diocese of Corpus Christi.