Opened in 1936 and sited on seven acres in City Park within a large stand of live oaks, the botanical garden was part of the park’s development under the Works Progress Administration (WPA). The classical garden’s irregularly-shaped site was designed by William Wiedorn, with architect Richard Koch and Art Deco artist Enrique Alferez, and included the Conservatory of the Two Sisters, a reflecting pool, a rose garden, and four large garden rooms. Each room is centered on a mature live oak and is planted with distinctive collections of plants. The rooms are divided along a central grass runway anchored by the Conservatory at one end and the Pavilion of the Two Sisters at the other. Two large rose arbors and a yaupon holly hedge enclose the Parterre Rose Garden, which is filled with rose beds divided by brick paths that intersect at a small round fountain. The garden remains a rare example of Art Deco and WPA-era public garden design.

In the early 1980s the garden was renamed the New Orleans Botanical Garden, with a focus on diversifying the horticultural collections. Now twelve acres, the garden’s boundary expanded in the 1990s to accommodate the Pavilion of the Two Sisters, an azalea and camellia garden, a Japanese garden and a historic train garden. In 2005, Hurricane Katrina put the garden under four feet of water, destroying all plant life except the live oaks. The garden was almost immediately rehabilitated, becoming a symbol of recovery for the city.