Nothing seemed more absurd than to see a colored man making himself ridiculous in order to portray himself.

—George Walker

George Walker began his career as part of a medicine show, which traveled to San Francisco in 1893. There, at age 20, he met Bert Williams and formed a vaudeville act. Walker was in charge of the team's business arrangements; Bert Williams reputedly said once, "It's a shame to take the money, so make the stakes small, George."⁵⁴ The act toured with several minstrel troupes and vaudeville shows. Touring in Chicago in the mid-1890s, they found themselves abruptly out of work when their vaudeville show suddenly ended. There they formed a routine in which Williams played the straight man and Walker delivered the punch lines. They took the show to New York and performed in The Gold Bug. Their performance in The Gold Bug gained them exposure and the two went on to join several white comedic acts until 1897, when they joined Will Marion Cook's all black company to perform in Clorindy. In 1898 Walker met his future wife Aida Overton, a singer and dancer in the Hurtig & Seamon variety troupe. The two married in 1899 and Overton became a star in her own right, featured in virtually all of the Walker and Williams comedies. She had studied dance from an early age and spent a brief period with Black Patti's Troubadours. She became the resident choreographer for the Wiliams and Walker productions, making her the first major black female choreographer. Overton was regarded as the best black female dancer in the America. In addition to choreographing and dancing, she performed in Cole and Johnson's The Red Moon in 1908, and S.H. Dudley's His Honor the Barber in 1911⁵⁵.

The Williams and Walker team had a string of hits with The Policy Players in 1899 and The Sons of Ham 1900. Yet it was their performance in the Will Marion Cook's production, In Dahomey in 1902 that made theater history and transformed them into international stars. The opening of this show on February 18, 1903 marked the first time a full-length African American musical comedy in three acts appeared on a Broadway stage. Following a run of 53 performances, the show traveled to England, where it remained for two seasons. Upon returning to the United States, the Williams and Walker company took In Dahomey on tour for the 1904-1905 season.

Williams and Walker switched managers and organized another successful production, Abyssinia, in 1906. Walker was the creative force behind Abyssinia, which featured avant garde lighting and elaborate set design and costumes. In 1908, Walker led the founding of The Frogs Club. The organization first met at Walker's home at 52 West 133rd Street in Harlem. Initially an organization for African American men in theater, it soon expanded its membership to black doctors and lawyers. Bob Cole, Lester A. Walton, James Reese Europe, Alex Rogers, Tom Brown, J. Rosamond Johnson, Jesse Ship, and R.C. McPherson (Cecil Mack) were among the initial members. Walker directed the Frogs Club (or Frogs as they were known), raising money for charities, maintaining theater space in Harlem and organizing events such as "The Frolic of the Frogs," an annual dance and vaudeville review, which took place monthly in August. The success of the Frogs Club was one of Walker's last triumphs. After falling ill during the production of the final Williams and Walker show, Bandanna Land (1907) Walker retired from show business. He died only a few years later, in 1911⁵⁶.