Madam Walker was born in Delta, Louisiana, on the Burney family plantation; her name was originally Sarah Breedlove. Walker's parents were ex-slaves who had both died by the time Sarah was seven. Sarah was married at age fourteen to Moses McWilliams. Widowed at age 20, she moved to St. Louis, Missouri, and supported her daughter, Lelia, by washing laundry.

In 1905, she moved to Denver, Colorado, and married Charles Joseph (C.J.) Walker, a newspaper sales agent; they were divorced in 1912, but she kept his name. Madam Walker started her cosmetics business in 1906. Her first product was a scalp treatment that used petrolatum and sulphur to heal scalp disease and to grow hair. She also softened the hair with an ointment she called Glossine, and straightened the hair with a metal comb. She did not, however, invent the comb.

She added Madam to her name and began selling her new "Walker System" door-to-door. Walker soon added other cosmetic products to her line. The products were very successful and she soon had many saleswomen, called "Walker Agents," who sold her products door to door and through beauty salons. In 1917, her agents came together in one of the nation's first convention of businesswomen. She settled briefly in Pittsburgh in 1908, then established her permanent headquarters in Indianapolis, Indiana, in 1910.

Madam Walker eventually became a millionaire from her business, which was at its peak from 1911 through 1922; she employed thousands of people. Walker moved to New York in 1916 and became active in influencing the arts and philanthropy. She contributed to many organizations ad educational institutions, including the NAACP, the Tuskegee Institute, Bethune-Cookman College, the YMCA and the YMCA. She also helped spur the Harlem Renaissance through her support of black artists and musicians. The Madam C. J. Walker Manufacturing Company is no longer in business.