Walk Two Moons tells the story of Salamanca (Sal) Tree Hiddle as she takes a trip with her grandparents from Euclid, Ohio, to Lewiston, Idaho, to visit her mother's grave. Along the journey, she tells them the story of Phoebe Winterbottom, a girl she befriended when Sal and her father moved from Kentucky to Ohio after the death of her mother. The one thing Phoebe and Sal have in common is the absence of their mothers; Phoebe's mother unexpectedly disappeared one day. We later find out the truth about Mrs. Winterbottom when it is revealed that she has an illegitimate son referred to as the "lunatic" by Phoebe and Sal. The family accepts her explanation and is reunited.

During this journey, Sal's grandmother is bitten by a snake in South Dakota. Her health begins to fail at this point, and by the end of the story, she has passed away. Eventually, Sal does manage to reach Idaho and visit the grave of her mother, who died when the bus she was traveling in went off the road. At the end of the novel, Sal and her father move back to Kentucky, where they begin to rebuild their lives. Sal, having received a sense of closure, is now more hopeful about the future.

Sal, a young Native American girl, is on a journey with her grandparents, tracing the journey of her absent mother, Sugar. Having been removed from her rural environment into city life, she struggles to adapt to school and her father's dating. On her journey, she tells her grandparents  tales about Phoebe Winterbottom, her best friend, and Phoebe's unusual family. During the trip, Sal's grandmother is taken ill and must be hospitalized. Her grandfather allows Sal to continue her journey to Lewiston, the destination of her mother. There she finds the wreckage of her mother's vehicle, and with the help of a peace officer, finds her mother's grave. This seemingly fruitless journey becomes one of discovery in the knowledge that her mother's spirit is alive in the earth and within herself.