Don Mitchell grew up in Hilo, on the island of Hawai‘i, and graduated from Hilo High School. He studied anthropology, evolutionary biology, and creative writing at Stanford and earned a Ph.D. in anthropology from Harvard. He lived among the Nagovisi people of Bougainville for several years in the 1960s and 1970s. For many years he was a professor of anthropology at Buffalo State, a unit of the State University of New York. He lived in Buffalo and later in Colden, New York, where he and the poet Ruth Thompson lived before they returned to his childhood home in Hilo. In mid-2020 they left Hilo for Ithaca, New York.  His stories have won praise from many quarters, including a Pushcart nomination and awards from the Society for Humanistic Anthropology, New Millennium Writings and other journals.

His collection of linked stories (A Red Woman Was Crying) was published in 2013 and revised and expanded in 2019. In 2020 he published the memoir Shibai: Remembering Jane Britton's Murder. His photographs have won competitions and have hung in several Hawai‘i galleries. He designs books for several small publishers. He has been an Artist in Residence for the City of Portales, New Mexico, and in 2019 shared (with Ruth Thompson) the Jack Williamson Visiting Professor of English Chair at Eastern New Mexico University.