In 1912, the vicariate was raised to the rank of diocese, with Corpus Christi designated as the Diocesan See. Bishop Verdaguer was succeeded by Bishops Paul Joseph Nussbaum (1913-1920), Emmanuel Ledvina (1921-1949), and Mariano Garriga (1949-1965). After the death of Bishiop Garriga, the bottom four counties of the diocese were separated to form the Diocese of Brownsville. Bishop Thomas J. Drury (1965-1983) became the fourth bishop of Corpus Christi; and the former Auxiliary Bishop of Corus Christi, Most Rev. Adolf Marx, was appointed as the first bishop to the newly formed Diocese of Brownsville. It was under Bishop Drury that the county of Goliad was separated from the Diocese of Corpus Christi at the time of erection of the Diocese of Victoria in 1982.
Bishop Rene H. Gracida next served as the Shepherd of the Diocese of Corpus Christi from July 11, 1983 through April 1, 1997. Bishop Gracida issued the decree of erection of the Western Vicariate of the Diocese of Corpus Christi to promote the pastoral good and unity of all the people of God in this area. The Western Vicariate encompassed the counties of Webb, Zapata, Jim Hogg, and the southern portion of La Salle County, which on August 9, 2000, officially separated from the Diocese of Corpus Christi to become the Diocese of Laredo.
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 González worked toward consolidating the diocesan infrastructure and uniting the faithful throughout the diocese. He stressed that the present era is one of hope. He became Apostolic Administrator of the Diocese of Corpus Christi and Archbishop of San Juan de Puerto Rico on May 8, 1999.
Bishop Edmond Carmody was installed as the seventh Bishop of the Diocese of Corpus Christi on March 17, 2000. With a vision and a passion to promote Catholic education in the region, on December 2005, Bishop Carmondy announced the creation of the first diocesan Catholic high school named after Blessed John Paul II to provide an opportunity for parents to give their children a Catholic education while experiencing the presence of the Holy Spirit. The high school officially opened its doors on August 1, 2006.