Cullen Bohannon, a former soldier and slaveholder, follows the track of a band of Union soldiers, the killers of his wife. This brings him to the middle of one of the biggest projects in US history, the building of the transcontinental railroad. After the war years in the 1860s, this undertaking connected the prospering east with the still wild west.

The story throws Elvis impersonators, Indians, modern cowboys, a 6-foot-tall blond assassin, a frat boy, a corrupt sheriff and a prostitute into a chase for a priceless American Indian artifact stolen during a poker game at an Indian casino.

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...