The first Catholic priests in Mississippi were French Jesuit and Capuchin missionaries who accompanied the La Salle, Marquette, and d'Iberville expeditions in the 17th and 18th centuries.

In 1787, three priests, Fathers McKenna, White, and Savage, arrived in Natchez from Spain and erected three missions in the vicinity.

These missions disappeared after the Spanish Empire ceded the area to the new United States in the early 19th century.

In 1837, Pope Gregory XV elevated the vicariate to the Diocese of Natchez, encompassing all of Mississippi.

When Bishop John J. Chanche of Natchez visited the Mississippi Gulf Coast in 1841, there were no Catholic churches or schools anywhere in the state.

The first Catholic church in Biloxi, Nativity Blessed Virgin Mary (BVM), was constructed in 1843.

[5] St. Stanislaus College, a boarding school for boys, was established in 1854 in Bay St. Louis by the Brothers of the Sacred Heart.

[20] Bishop Kihneman acknowledged three of these names as credibly accused of sexual misconduct of minors in 2019, but recognized that this was a “small, belated step forward.” [21] The following priests were listed by the diocese as having credible accusations of sexual abuse of minors.

In 2019, the diocese was sued by man who claimed that he had been sexually assaulted when he was 12 years old in the mid-1980s by Reverend John Scanlon, then serving at Sacred Heart Church in Hattiesburg.