Encouraged by Winold Reiss, with whom he studied in New York, Douglas explored African themes and sought to make his cultural heritage relevant to contemporary African-American experience. For this, he won critical praise and attention, and was dubbed the father of black American art. " His illustrations appeared with Reiss's in the 1925 book, The New Negro; this volume is said to have played an important role in giving an identity to the literary circle of the Harlem Renaissance. As a member of the Renaissance circle, Douglas illustrated books by Countee Cullen, Langston Hughes, and James Weldon Johnson. His illustrations also appeared in Vanity Fair, Theatre Arts, and American Mercury. His other well-known works include murals at Fisk University, the Harlem branch of the Y.M.C.A. at 180 West 135th Street, and Harlem Hospital, and canvases for the Countee Cullen branch of the new York Public Library of West 136th Street: Africa, Slavery, Reconstruction, and Metropolis.

Douglas and his wife, Alta, lived on Strivers' Row at 227 West 139th Street in the 1920s but moved to 409 Edgecombe Avenue in 1932, where they were popular hosts to Harlem's cultural elite. Said Arna Bontemps "Everybody dropped in; this was really a meeting place for all the artists and intellectuals in Harlem....The apartment was decorated with Douglas's own paintings. It almost became a hallmark of the Harlem period in literature to have a book jacket by him." Alta Douglas died in 1958. Aaron Douglas lived in Nashville full-time after his retirement from Fisk University in 1966.