After grade school Wright attended Lanier High School but dropped out after a few weeks to work; he took a series of odd jobs to save enough money to leave for Memphis, which he did at age seventeen. While in Memphis he worked as a dishwasher and delivery boy and for an optical company. He began to read contemporary American literature as well as commentary by H. L. Mencken, which struck him with particular force. As Wright reveals in his autobiography Black Boy, he borrowed the library card of an Irish co-worker and forged notes to the librarian so he could read: "Dear Madam: Will you please let this nigger boy have some books by H. L. Mencken?" Determined to leave the South before he would irretrievably overstep the bounds of Jim Crow restrictions on blacks, Wright took the train to Chicago in December 1927.

In Chicago Wright worked at the post office, at Michael Reese Hospital taking care of lab animals, and as an insurance agent, among other jobs. There, in 1932, he became involved in the John Reed Club, an intellectual arm of the Communist party, which he joined the next March. By 1935 he found work with the Federal Negro Theater in Chicago under the Federal Writers' Project. He wrote some short stories and a novel during this time, but they were not published until after his death. In 1937 Wright moved to New York City, where he helped start New Challenge magazine and was the Harlem editor of the Daily Worker as well as coeditor of Left Front. Wright's literary career was launched when his short story collection, Uncle Tom's Children (1938), won first prize for the Story magazine contest open to Federal Writer's Project authors for best book-length manuscript. Harper's published this collection with "Fire and Cloud," "Long Black Song," "Down by the Riverside," and "Big Boy Leaves Home"; in 1940 the story "Bright and Morning Star" was added, and the book was reissued. Native Son followed in 1940, the first bestselling novel by a black American writer and the first Book-of-the-Month Club selection by an African-American writer. It sold 215,000 copies in its first three weeks of publication. Native Son made Wright the most respected and wealthiest black writer in America; he was awarded the National Association for the Advancement of Colored People's prestigious Spingarn Medal in 1941. After Uncle Tom's Children, Wright declared in "How Bigger Was Born" that he needed to write a book that bankers' daughters would not be able to "read and feel good about," that would "be so hard and deep that they would have to face it without the consolation of tears"; Native Son is uncompromising.

In Native Son, Wright presents his guilt-of-the-nation thesis. His main character, Bigger Thomas, is a nineteen-year-old edgy small-time criminal from Chicago's South Side ghetto. The novel races with no stops in between the three parts: Book I, Fear; Book II, Flight; and Book III, Fate. When Bigger is offered a job as a chauffeur for a wealthy white family, he imagines himself in various fanciful scenarios, including sexual ones with the daughter. Lines that referred to Bigger's sexual interest in Mary Dalton were taken out in 1940 and only restored fifty-three years later in the 1993 Library of America edition, edited by Arnold Rampersad and copyrighted by Wright's second wife, Ellen Wright. Bigger's first driving job requires him to take Mary to pick up her communist lover, Jan Erlone, then eat with the couple in a black diner on the South Side. They drink themselves into oblivion on the ride home and invite Bigger to join them. Jan leaves, and Bigger must take Mary home and put her in bed. Terrified to be in Mary's bedroom and afraid to be caught as he is kissing her, he puts a pillow over her face when her blind mother walks in. Realizing he has accidentally murdered her, he drags her in a trunk to the basement and burns her in the furnace. Bigger rationalizes, correctly for a while, that the whites will never suspect him because they