Beginning just after the bloody Sioux victory over General Custer at Little Big Horn, Bury My Heart at Wounded Knee intertwines the perspectives of three characters: Charles Eastman, né Ohiyesa, a young, Dartmouth-educated, Sioux doctor held up as living proof of the alleged success of assimilation; Sitting Bull, the proud Lakota chief who refuses to submit to U.S. government policies designed to strip his people of their identity, their dignity and their sacred land - the gold-laden Black Hills of the Dakotas; and Senator Henry Dawes, who was one of the architects of the government policy on Indian affairs. While Eastman and patrician schoolteacher Elaine Goodale work to improve life for the Indians on the reservation, Senator Dawes lobbies President Grant for more humane treatment, opposing the bellicose stance of General William Tecumseh Sherman. Hope rises for the Indians in the form of the prophet Wovoka and the Ghost Dance...

Nate Burns, a former Baltimore city homicide detective, is the new police chief in sleepy Lunacy, Alaska. The job comes with a free room in the 'lodge', the town's multi-purpose inn, pub etcetera run by 'loose' flirter Charlene Galligan. Sole deputy Otto Gruber is among the failed local applicants. Shortly after Nate gets on sensual-bickering terms with Charlene's fickle, estranged daughter, pilot Meg, lost mountaineers find the frozen corps of Meg's dad Pat, missing for 15 years. State police sergeant Coben dubiously claims jurisdiction and flies out the body. Nate soon discovers nothing is as it seems after Lunatic newspaper editor Max Hawbacker is found shot, with a fake suicide PC note 'I killed Pat'. Uncovering more past secret proves dangerous for dogs, Nate and his job.