The Cherokee Garden Club of Atlanta, Georgia, was formed on March 10, 1928 and is Atlanta's second oldest garden club. The club was organized with the original purpose of "the study and culture of flowers, landscape gardening, protection of natural trees, plants, and birds, and the encouragement of civic planting." In 1928, the club was one of the eleven founding clubs of The Garden Club of Georgia, Inc. The club was also one of the founding clubs of the Atlanta Garden Center and the Atlanta Flower Show Association. In 1963, the club was invited to join the Garden Club of America. The club is also a member of the National Council of Garden Clubs, Inc., the Georgia Conservancy, Inc., and the National Trust for Historic Preservation. The club is governed by elected officers such as president, vice-president, and treasurer.

Cherokee Garden Club's first civic project was the planting of the Dolly Blalock Black Memorial Garden at Egleston Hospital on Forrest Avenue, Atlanta, in 1928, designed by Norman C. Butts. In 1959, the Hospital moved to Clifton Road and the club hired landscape architect Edward L. Daugherty to design a new garden, which the club maintained. In 1956, the club began an annual project lasting through 1967, "Christmas Trees Around the World," where decorated trees were on public display to promote peace and goodwill between nations. The proceeds of this project allowed the club to take on other civic projects such as the restoration of the 18th century Boxwood and Kitchen Gardens at the Thornton House (1962-1966), the development of the Swan House Courtyard Garden at the Atlanta Historical Society (now known as the Atlanta History Center), and the funding of projects at the Atlanta Art Association (now known as the High Museum of Art). Prior to the founding of the Atlanta Botanical Garden, the club hired Edward L. Daugherty in 1969 to design a garden for the blind called the Fragrance Garden in Piedmont Park with club member Eleanor Morgan Montgomery. Under the direction of club member Sarah Patten Gwynn, the garden was refurbished in 1973 and expanded into the "Fragrance and Texture Garden," which was later incorporated into the Atlanta Botanical Garden, and maintained by the club for many years. In 1973, the club jointly published with the Peachtree Garden Club, Architecture of Neel Reid in Georgia by James Grady.

In 1975, under the leadership of past club president Anne Coppedge Carr, the club established the Cherokee Garden Library, housed at the Atlanta Historical Society (now known as the Atlanta History Center) to serve as an educational repository for garden and horticultural records for the Southeast. In 2001, the Garden Club of America awarded Anne Carr the prestigious Amy Angell Collier Montague Medal for "outstanding civic achievement" for the creation and development of the Cherokee Garden Library. Under the leadership and with support of the club since 1975, the Cherokee Garden Library is part of the Kenan Research Center at the Atlanta History Center and is one of the premier horticultural libraries in the country with a collection of over 28,000 books, photographs, manuscripts, seed catalogs, and landscape drawings. The club has also initiated many other conservation, art, and educational projects. The club has supported numerous other organizations, such as the Veterans Hospital, the American Red Cross, the Atlanta Speech School, and the Atlanta Botanical Garden. In 2008, the club founded the Cherokee Garden Club Community Fund "to protect, improve, and restore the environment of the surrounding community through programs and actions in the field of education and conservation." Grant recipients have included organizations such as the Cherokee Garden Library, Georgia Organics, Louise Howard Park, Peachtree Battle Neighborhood Improvement, and Trees Atlanta.

Cherokee Garden Club has participated in numerous flowers shows beginning in 1929, with Peachtree Garden Club's annual flower show. The club competed in the first citywide flower show in 1934, winning the most awards of any club. The club has continued to actively participate and host flower shows and exhibitions, winning numerous awards, both nationally and internationally, while pursuing the horticultural study of flower arrangements. The club has been active member of the Garden Club of America, with club members serving on many committees in Zone VIII and on the national level. The club also hosted many zone and annual meetings for the Garden Club of America.