Once Upon a River is the story of Native American teenager Margo Crane in 1970s rural Michigan. After enduring a series of traumas and tragedies, Margo (newcomer Kenadi DelaCerna) sets out on an odyssey on the Stark River in search of her estranged mother. On the water, Margo encounters friends, foes, wonders, and dangers; navigating life on her own, she comes to understand her potential, all while healing the wounds of her past.