The story of Creek Mary's blood opens in 1905 at a White House luncheon hosted by Teddy Roosevelt in honor of Mary Dane, "a young Indian woman from Montana, the first of her race and the first of her sex to graduate from Columbia Medical College." A young reporter, who has been sent by his newspaper to cover the event, becomes fascinated with the story of Creek Mary and her descendants. He travels to Montana at the invitation of Dane, Creek Mary's grandson, to learn of the remarkable events which encompass five generations of Indian/American history, from pre-Revolutionary days, to the Little Big Horn, to Wounded Knee, and into the twentieth century. Dee Brown skillfully utilizes the flashback technique as Dane narrates his tale to the sympathetic reporter, now in the past and then in the present, blending the two into a well-developed narrative.

The dominant themes of Creek Mary's Blood are the displacement of the Indians and the treachery of the U.S. government in its dealings with the Indians. (p. 11)

Dee Brown uses a literary technique which has become increasingly popular in the past several years. He traces a family's history as that history relates to the major events of the times considered. Thus we see Creek Mary protesting Indian removal in the 1830s and her grandson Dane participating in and observing numerous confrontations in the West. (p. 24)

Creek Mary's Blood is rightly sympathetic to the Indian. It will correct many of the stereotypes which Anglo-Americans have about the Indians and their history. Few who read Brown's latest book will remain untouched by the panorama of events. It is an incredible, yet epic tale. (p. 25)