Brown (the author of Bury My Heart at Wounded Knee) keeps a tight focus in [Creek Mary's Blood], restricting his story to the life and descendants of a single woman, Creek Mary (Akusa Amayi), but tracing them through five generations and across most of the American continent…. Using fictional characters against a carefully researched historical background, he combines the attractions of both genres. The major incidents of his story are true, but by inventing fictional participants he is able to give the events a human dimension lacking in the historic record, which is relatively cold and mostly recorded from the white man's point of view.

Brown's prose style is as much that of the historian as of the novelist—not dazzling, and poetic only in occasional quotes which capture the special rhetoric embedded in the structure of Indian languages, but efficient, informative and readable.

Mary had two husbands who symbolize two ways of dealing with the cultural clash that is the book's subject. The first was an English colonist, John Kingsley, who is related thematically to the effort at accommodation and assimilation among the Cherokees in the Southeast. The second was a Cherokee, The Long Warrior, a leader of the resistance to white encroachment, whose offspring merged into the Cheyenne of the Central Plains, where that resistance was most bitter and prolonged.

Both ways of coping ultimately proved futile, and in his novel's epic length Dee Brown has leisure to examine the modes of futility in assimilation and in resistance. (p. 4)

All the greed, violence and deception that litter the pages of this novel, the cheating in the marketplace, massacres of the helpless and repeatedly broken treaties, can finally be summed up in one tiny image near the end of the book, when the Indian community is trying to raise money to put Creek Mary's last descendant, Amayi, through medical school. Even the children contribute, the boys making jewelry, arrows and arrowheads and selling them through the windows of trains stopped at the local depot.

"Sometimes the train would start up before they gave us money," a young Indian recalls. "We would run along on the cinders beside the train until it was going too fast for us, and the mean ones would laugh at us and keep our arrows and not give us money."

That's how the West was won. (p. 5)