Jacob Tao, a young Japanese American high school teacher from southern California, arrives in Fairbanks in 1968, the year a bonanza oil discovery was made on Alaska's North Slope. He moves into an apartment next door to an elderly, reclusive woman, Lydia Galloway. After she falls and breaks a hip, Jacob discovers she has ties with no one in town, forcing him to become her caregiver for one summer. Sympathetic toward the lonely woman, he reluctantly agrees to search for the son, Isaiah John, who she hasn't seen in over 20 years. While she is recovering, Lydia intrigues Jacob with anecdotes of her clandestine escape to Alaska in the 1920s and her life as a trapper's wife in the rugged Kantishna Hills near Mt. McKinley. The fact that her missing son is rarely mentioned in these stories frustrates Jacob at first, and then makes him even more curious about Isaiah's whereabouts. He jumps at the chance to teach for a year at an Athabascan village on the Tanana River, anticipating it might be just the place to find out about the mysterious Isaiah John. Jacob's personal life takes a dramatic turn in the village, where he meets the Williams sisters, Rachel and Ruby, and becomes friends with Alice Schmidt, the alcoholic wife of the head teacher at the village school. Searching for Isaiah John is a story within a story. Told primarily from the perspective of Jacob Tao in the late 1960s, it interweaves accounts of Isaiah's disappearance from the viewpoint of Lydia as well as her old flame, Michael Tailor, who spent decades in his own pursuit of the missing man. The Tanana River, with its braided channels and hidden sloughs, form the backdrop of this tale about the meaning of cultural identity.