Not Without Laughter portrays African-American life in the 1910s, focusing on character development rather than plot. However, the main storyline focuses on Sandy's "awakening to the sad and the beautiful realities of black life in a small Kansas town." The major intent of the novel is to portray Sandy's life as he tries to be the best he can be, aspiring to folks such as W. E. B. Du Bois and Booker T. Washington.
Hughes said that Not Without Laughter is semi-autobiographical, and that a good portion of the characters and setting included in the novel are based on his memories of growing up in Lawrence, Kansas: "I wanted to write about a typical Negro family in the Middle West, about people like those I had known in Kansas. But mine was not a typical Negro family."