Despite her wealth, Ms. Malone lived conservatively and gave away much of her fortune to help other African Americans. She is one of America's first major black philanthropists. Malone donated large sums to countless charities. At one time, it is believed that she was supporting two full-time students in every black land-grant college in the United States. She gave $25,000 to the Howard University Medical School during the 1920s that, at the time, was the largest gift the school had ever received from an African American. She also contributed to the Tuskegee Institute. Malone was also generous with family and employees. She educated many of her nieces and nephews and bought homes for her brothers and sisters. She awarded employees with lavish gifts for attendance, punctuality, service anniversaries, and as rewards for investing in real estate.
A $25,000 donation from Malone helped build the Pine Street YMCA. She also contributed to several orphanages and donated the site for the St. Louis Colored Orphans' Home. She raised most of the orphanage's construction costs and served as board president for the home from 1919 to 1943. The home was renamed the Annie Malone Children's Home in 1946.
As the Black population of St. Louis increased by sixty percent, Barnes Hospital was still segregated with no facilities for Black patients or staff. Consequently, Annie Malone donated $10,000 toward the development of a maternity ward for Black women.