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A fire on March 21, 1788, started when a candle ignited the lace draperies of an altar in the home of the military treasurer of the colony, Vincente Jose Nunez, on Chartres Street. Among the buildings burned to the ground were the Church of St. Louis, the priests' residence, and the Casa Principal, which housed the Cabildo.

In a letter written on March 28, 1788, Father Antonio de Sedella (Pere Antoine), who was pastor of the church, described the rapidity with which the fire made headway. He wrote that he had sent some of the church records to the home of the tobacco director, "distant from the Presbytere about two rifle shots," but they were lost when that house caught fire.

Nearly a year elapsed before the charred remains of the church were cleared away and construction of a new church began in early 1789. More than five years were to pass before the new church was completed in December, 1794.

The Good Friday fire began about 1:30 p.m. at the home of Army Treasurer Don Vincente Jose Nuñez, 619 Chartres Street, corner of Wilkinson,[1] less than a block from Jackson Square (Plaza de Armas). Because the fire started on Good Friday, priests refused to allow church bells to be rung as a fire alarm.[2] Within five hours it had consumed almost the entire city as it was fed by a strong wind from the southeast. The fire destroyed virtually all major buildings in the then-city (now French Quarter), including the church, municipal building, army barracks, armory, and jail. Colonial Governor Esteban Rodríguez Miró set up tents for the homeless.