One of the best known of the six nations is the Seneca, and arguably the most famous Seneca chief was Ely Samuel Parker. Over the course of his life, he was a Seneca chief, a civil engineer, a close friend and adjutant to General Ulysses S. Grant, an advocate for the Indian peoples, and the first Native American Commissioner of the Department of Indian Affairs. His marriage to a much younger socialite scandalized Washington, and he made a fortune on Wall Street and lost it all. He ended his life in genteel poverty, working for nearly 20 years in an obscure position for the New York City Police Department.

Parker was a largely self-taught engineer, who worked on various canal projects, and was hired by the Department of the Treasury to supervise the construction of several buildings in Galena, Illinois, where he met a shy salesclerk named Ulysses S. Grant. At the age of 18, he dined with President Polk, later talked with President Lincoln, and had the commanding general of the U.S. Army as the best man at his wedding. He was the principal source for the first serious ethnological work by one of the first American ethnologists, who dedicated the book to Parker. He was a plaintiff before the U.S. Supreme Court when he was in his teens and was so important in the Seneca's struggle to retain their Tonawanda reservation that he was made grand sachem-principal chief-in his early 20s. He tried twice to join the Union forces but was rejected, being told it was a "white man's war." He was only able to join the Army through the influence of Grant and another general. His most famous moment came during the surrender of General Robert E. Lee's Army of Northern Virginia at Appomattox. He transcribed and copied the surrender documents which were signed by Lee and Grant, and he shook hands with Lee, who said to Parker, "It is good to see an original American here." To that, Parker responded "We are all Americans."

The total population of Indian Territory in 1861 was about 100,000. There was a small population of non-Indians that included tradespeople, missionaries, blacksmiths and so on, the largest of which were about 8,000 slaves. An unknown number of free blacks lived in the territory, and some of the Indian groups were racially mixed. Most of the population was settled, meaning that subsistence farming, ranching, and even plantation agriculture were all to be found. The far western region of the territory was nearly empty, but sometimes frequented by Plains Tribes. In general, the pre-War Indian inhabitants were probably the most prosperous and safest of all the country's Indians.

About 10,000 Native Americans are thought to have died in Indian Territory as a result of the Civil War, including soldiers, but also as a consequence of a total breakdown of law and order and chronic guerilla war. That estimate could be low, because the Cherokee population alone dropped from 21,000 before the Civil War to 15,000 after it.

Stand Watie's life connects the traditional Cherokee homeland in Tennessee and Georgia, the fight within the tribe over leaving for the West or staying on their homeland and trying to resist, and the Trail of Tears. At the same time, his life also includes the ongoing split between mixed-blood and full-blood Cherokee in the Cherokee Nation, and the chaos of Indian Territory during the Civil War.

Like the country as a whole, the Cherokee Nation was split over the question of slavery, and with an estimated 100 slaves owned, Watie was the biggest native slaveholder in the region. At the start of the war, Watie was commissioned as a colonel in Confederate service and later as a brigadier general. His 1st Cherokee Mounted Rifles Regiment fought more engagements than any other Confederate unit west of the Mississippi River. As a result, Watie is perhaps the most famous figure of a widely overlooked aspect of the Civil War.