Yonnondio follows the heartbreaking path of the Holbrook family in the late 1920s and the Great Depression as they move from the coal mines of Wyoming to a tenant farm in western Nebraska, ending up finally on the kill floors of the slaughterhouses and in the wretched neighborhoods of the poor in Omaha, Nebraska.

Mazie, the oldest daughter in the growing family of Jim and Anna Holbrook, tells the story of the family's desire for a better life – Anna's dream that her children be educated and Jim's wish for a life lived out in the open, away from the darkness and danger of the mines. At every turn in their journey, however, their dreams are frustrated, and the family is jeopardized by cruel and indifferent systems.