The museum is home to the single largest public repository of works by Henry Darger (1892–1973), one of the most significant self-taught artists of the 20th century.

Darger created nearly 300 watercolor and collage paintings, bound into three huge volumes, to illustrate his epic masterpiece, The Story of the Vivian Girls, in What Is Known as the Realms of the Unreal, of the Glandeco-Angelinnian War Storm, Caused by the Child Slave Rebellion, a tale about a world torn apart by war. Darger began to work on In the Realms of the Unreal (as it is commonly called) when he was about 19 years old. When it was completed, after decades of work, the typewritten manuscript was 15,145 pages long and comprised 13 volumes. In the Realms of the Unreal is the tale of seven little girls—the Vivian Girls—who set out to rescue abducted children who have been enslaved by the adult Glandelinians. The heroes in this tale are always the children, the villains typically adults. The story of war and peace, of good versus evil, loosely parallels many of the events of the American Civil War. Darger was a Civil War enthusiast, and he chronicled the flags, maps, and officers in separate journals. In his version of the conflict, the enslaved people are white children who usually appear unclothed—Darger poignantly captured the powerlessness of any enslaved peoples by depicting them as young, innocent, and naked. The nakedness of the children also exposes their mixed gender, which is a compelling aspect of the artist's imagery, open to many interpretations. Throughout the tale, one confronts much death and destruction, and, as is often the case in the world of fiction, good usually triumphs over evil—but not without challenges along the way. In the Realms of the Unreal, however, has two endings: in one, concluding a series of harrowing trials and complex adventures, the heroic Vivian Girls emerge triumphant, while in the other, they are defeated by the evil Glandelinians. The fantastic watercolors accompanying the narrative, which are executed in lyrical seductive hues and measure up to 12 feet in width, are among the works by Darger that are most celebrated today.

Above: Untitled (Idyllic Landscape with Children) (detail) (double-sided), Henry Darger (1892–1973), Chicago, mid-twentieth century, watercolor, pencil, carbon tracing, and collage on pieced paper, 24 × 106 1/2", museum purchase with funds generously provided by John and Margaret Robson, 2004.1.3b.