The novel features Lucky, a 10-year-old girl who lives in a small town called Hard Pan (population 43) in the California desert with her two friends Lincoln, who is an avid knot tyer and expected by his mother to be the president when he grows up, and Miles, a five-year-old whose favorite book is "Are You My Mother?" by P.D. Eastman.
After her mother died two years ago from being electrocuted, her father called upon his first ex-wife, Brigitte, to come to the United States from France to take care of Lucky. Lucky fears that Brigitte is tired of being her guardian and of their life in Hard Pan. When she discovers Brigette's suitcase and passport lying out, she becomes convinced that Brigitte will abandon her and return to France. This anxiety prompts Lucky to seek help from her "Higher Power", a notion she gets from eavesdropping at her town's 12-step meetings.
After discovering three "signs" to leave, she runs away with her dog, HMS Beagle, during a sandstorm. Outside of town, however, she finds Miles, lost and injured in the storm, and takes him with her. They take shelter in the dugouts near an abandoned mine and wait out the storm. They are soon joined by Lincoln, who tells them that the rest of the town is looking for them, and will be there shortly. Before she leaves the dugouts, she casts her mother's ashes out in the wind in a makeshift memorial service with the townsfolk.
Brigitte takes Lucky home and explains the papers Lucky had found in Brigitte's suitcase were actually to legally adopt Lucky, and reveals her plans to open a restaurant in Hard Pan.