An 1848 city legislature act allowed the Catholic wardens to establish a new cemetery. Land along Bayou St. John, purchased from Evariste Blanc for $15,000, became St. Louis Cemetery #3. The cemetery opened in 1854.
The original plans for the cemetery called for three main aisles named for St. Peter, St. Paul and St. Louis along with four smaller aisles named for St. Mary, St. Joseph, St. Magdalene and St. Philomene. In 1865 J.A. d'Hemecourt developed a new plan to increase the depth of the burial ground and creating cross aisles which were named for bishops and archbishops of the diocese.
The cemetery is the last resting place for several notable New Orleanian including; the family tombs of several restaurateurs such as the Galtoire, Tujague, and Prudhomme, architects James Gallier and James Gallier Jr., and photographer E. J. Bellocq.