St. Louis Cathedral in New Orleans is the spiritual anchor of the famed French Quarter. The existing building borders Jackson Square on the site where New Orleanians have worshipped since 1727. It was designated as a church site on March 29, 1721, by the French engineer Adrien De Pauger as part of the plan of the Louisiana engineer-in-chief, LeBlond de la Tour, who was at the capital of Biloxi.

The original parish church was dedicated to Louis IX, the king of France turned saint, was perhaps the first building in New Orleans of so-called �brick between posts� construction, an architectural method used in Louisiana until at least the mid-19th century. De Pauger died on June 21, 1726, before the church was completed.

That structure stood for 60 years, during which time there worshipped within its walls French Governors Perier, Bienville, Vaudreuil and Kerlerec and Spanish Governors Unzaga, Galvez and Miro. 

However, on March 21, 1788, a candle ignited the lace draperies of an altar in the home of the colony's military treasurer (Vincente Jose Nunez) on Chartres Street. The Church of St. Louis, the priests' residence and the Casa Principal (that housed the Cabildo) burned to the ground in the ensuing fire. Almost a year passed before the church's remains were cleared, and new construction began in early 1789.

Shortly before the completion of the church on April 25, 1793, the diocese of Louisiana and the Floridas was created by Pope Pius VI. Don Luis Ignacio Maria de Pefialver y Cardenas of Havana was appointed the first bishop with New Orleans as his See city. Therefore, the new church was dedicated as a cathedral, Services began there on Christmas Eve 1794.