After mastering an Academic Realist style as a teenager, Alston became increasingly interested in African art and aesthetics while in graduate school at Columbia University Teacher's College. After graduating, he remained in Harlem and cofounded the Harlem Art Workshop in 1934. In response to a need for additional space, he secured a facility at 306 West 141st Street, or "306," which would serve as a center for creative minds in Harlem, including Ralph Ellison, Augusta Savage, and Richard Wright.
In 1935, Alston became the first Black supervisor for the Federal Art Project when he received an assignment to direct the Works Progress Administration (WPA) murals in Harlem Hospital. The Federal Art Project approved his designs, which were heavily influenced by the work of Mexican muralism, jazz music, and Social Realism, but the hospital administration rejected the works for an excess of African American subject matter. The hospital eventually allowed production of the murals to proceed after protests and extensive press coverage and, in 1936, two were exhibited at the Museum of Modern Art. In response, Alston also cofounded the Harlem Artists Guild in the hope of convincing the WPA to fund more Black artists. In 1963, he became a founding member of Spiral, an artist collective that sought to contribute to the civil rights movement by increasing gallery and museum representation for Black artists.
