A French merchant in 1865 constructed the La Lomita Chapel in Mission, Texas, which in 1871 he bequeathed to the Missionary Oblates of Mary Immaculate.

That same year, The pope appointed Reverend Adolph Marx of the Diocese of Corpus Christi as the first bishop of Brownsville.

Marx died a few months later that year; Paul VI then named Reverend Humberto Medeiros of the Diocese of Fall River as his replacement.

The pope named Auxiliary Bishop John Fitzpatrick from the Archdiocese of Miami to replace Medeiros in Brownsville.

In November 2018, the diocese sued the Trump Administration, saying that the routing of its border wall with Mexico would cut off access to La Lomita Chapel.

In February 2019, Congress amended an existing appropriations bill to prohibit new funding for any border barriers at La Lomita.

In 2004, the Dallas Morning News published a report on sexual abuse accusations against Reverend Basil Onyia, a Nigerian priest.

Onyia arrived in Brownsville in 1999 and was assigned as assistant pastor of the Basilica of Our Lady of San Juan del Valle.

[11] Deacon Ronaldo Chavez, a school principal, was arrested in January 2014 on charges of sexually abusing a 15-year-old boy multiple times in 2013.

[13] The diocese was sued by two siblings in March 2019 who claimed they were sexually abused as young children by Reverend Benedicto Ortiz from 1982 to 1985.

[15] Mario Alberto Avilés (2018–present) Joseph Patrick Delaney, appointed Bishop of Fort Worth in 1981 Catholic Campus Ministry, University of Texas Rio Grande Valley St. Luke's School – Brownsville, closed 2020 The diocese's radio and television stations are operated under the license name of RGV Educational Broadcasting, Inc.[17]