The book's contents across many chronological chapters challenge what Dunbar-Ortiz articulates as the founding mythology of the burgeoning country, bolstered in the 19th century by the concept of Manifest Destiny and the Doctrine of Discovery.

It graphically depicts the seizure of the original inhabitants' territories and subsequent displacement and elimination of them through genocidal practices such as the movement to Kill the Indian, Save the Man.

[3] An Indigenous Peoples' History of the United States details how such policies, practices, and values were manifest through the ranks of the U.S. military to the highest offices of government.

She includes descriptions of extreme violence inflicted on civilian communities, the use of mercenary military leaders who had fought in the European wars of religion, and the practice of bounties for scalps which had precedent during the Plantations of Ireland.

Dunbar-Ortiz chronicles the role of Andrew Jackson in waging wars of annihilation against Native peoples east of the Mississippi, from 1801 when he commanded the Tennessee militia, through his years as US President.

The other major topic in this chapter is what Dunbar-Ortiz describes as the "reinvention of the birth of the United States" in the novels of James Fenimore Cooper and other writers of that era.

Dunbar-Ortiz describes the parallels between U.S. military methods used against Native peoples with those used overseas from 1798 to 1919, drawing on examples from campaigns in countries around the world, and asserting that these engagements were "all about securing markets and natural resources, developing imperialist power to protect and extend corporate wealth."

It then describes how the United Nations Study on Treaties, completed in 1999, has been used to bolster Indigenous claims for restoration, restitution, and repatriation of lands, such as in Cobell v. Salazar and the Black Hills lawsuit.

... For the future to be realized, it will require extensive educational programs and the full support and active participation of the descendants of settlers, enslaved Africans, and colonized Mexicans, as well as immigrant populations.

[6] A reviewer in CounterPunch wrote that this book "will be of great value to those first learning about the Indigenous perspective as well as someone like me who has been reading and writing about native peoples for the past twenty-five years.

"[7] Publishers Weekly found the book comprehensive, noting that "Dunbar-Ortiz brings together every indictment of white Americans that has been cast upon them over time, and she does so by raising intelligent new questions about many of the current trends of academia, such as multiculturalism.

The review added that "Ancestral Puebloan sites show evidence of cannibalism and torture, which in turn points to the inconvenient fact that North America was not an Eden before the arrival of the Europeans.