Spanish missionaries brought Roman Catholicism to Louisiana in the early 16th century, and many of them were killed in their attempts to convert the Indians. During the early days, the most active religious orders were the Jesuits, Capuchins, and Ursuline nuns. Until the Louisiana Purchase, the public practice of any but the Catholic religion was prohibited, and Jews were entirely banned.

Joseph Willis, a mulatto preacher who conducted prayer meetings at what is now Lafayette in 1804, organized the first Baptist church west of the Mississippi, at Bayou Chicot in 1812. In the Opelousas region, in 1806, the first Methodist church in the state was organized. The first Episcopal church was established in New Orleans in 1805, a Methodist church in 1813, a Presbyterian church in 1817, a synagogue in 1828, and a Baptist church in 1834. After the Civil War, blacks withdrew from white-dominated churches to form their own religious groups, mainly Baptist and Methodist.

As of 2000, the Roman Catholic Church was the largest Christian denomination, with 1,382,603 church members. The leading Protestant denominations were the Southern Baptist Convention, 768,587; the United Methodist Church, 160,153; Assemblies of God, 49,041; and the Episcopal Church, 33,653. There were about 16,500 Jews residing in Louisiana in 2000, a majority of them in New Orleans. The Muslim community had about 13,050 members. Voodoo, in some cases blended with Christian ritual, is more widespread in Louisiana than anywhere else in the United States, although the present number of practitioners is impossible to ascertain. Over 1.8 million people (about 41.2% of the population) did not claim any religious affiliation in the 2000 survey.