As the U.S. government and its citizens took possession of indigenous lands and resources, forced marches were used to remove indigenous peoples and open their lands for European-American settlement. Though a practice originating from the earliest years of contact, forced marches reached their zenith in the nineteenth century when dozens of such "removals" occurred, affecting tens of thousands of indigenous people and the transfer of millions of acres of land to nonindigenous ownership.

In this context, forced marches are connected to broader U.S. policies, such as removal and relocation, that were used as a means to control and confine indigenous populations by concentrating them into small geographic areas. The death toll among those who were force marched to new locations was sometimes as high as 50 percent, but the most devastating consequences of forced marches were long term. Removal required the dispossession of indigenous peoples from their lands and the subsequent loss of the ways of life associated with their attachment to a particular land base. The repercussions of this tremendous sense of loss have reached into the twenty-first century as indigenous populations generally continue to suffer high mortality rates and a poor quality of life.

The best-known forced march is the 1838 Tsalagi (Cherokee) Trail of Tears in which seventeen thousand Tsalagi were removed from their southeastern homes to Indian Territory. After they were rounded up and placed in stockades, the population was removed in more than a dozen groups. Most traveled over land in small groups averaging 1,000 people, forming long refugee columns and suffering from starvation, disease, exposure, hardship, and accidents. It is estimated that at least 4,000, and perhaps as many as 8,000 people died as a direct consequence of the forced removal and as many as half of the remaining population died within the first year after removal, largely due to disease. The extent of death and suffering as a consequence of the violent process of removal is not unusual, but is in fact characteristic of the forced marches experienced by indigenous peoples throughout American history.

The U.S. government carried out these brutal forced removals under the pretense of legality. After manipulating the Tsalagi population to obtain the signatures of a small, illegitimate faction, the United States ratified the Treaty of New Echota, which relinquished Tsalagi lands in the Southeast in exchange for lands in Indian Territory and $15 million. This bare semblance of legitimacy in dealings with indigenous peoples is all that remained after the passing of the Indian Removal Act of 1830 under President Andrew Jackson's administration. This Act authorized the president to exchange indigenous lands in the East for those in the West and to negotiate with tribes for their own removal. While the Act required indigenous agreement and support for removal, this aspect was ignored in practice. Furthermore, the U.S. government was indifferent to the fact that, in some cases, indigenous peoples already occupied lands in the West they were promising to others; this required taking land from some groups to make it available to others.

While Jackson has been associated most prominently with forced marches and acts of removal, he was not the first or last president to advocate indigenous removal. Early explorers such as Jacques Cartier, Martin Frobisher, and Henry Hudson practiced indigenous removal, as did early New England colonists who established "praying towns" and state reservations. Thomas Jefferson was a strong proponent of removal. He drafted a constitutional amendment, decades before Jackson, which would have allowed for the exchange of indigenous lands in the East for lands west of the Mississippi. In other contexts, he wrote that any Indians resisting American expansion should be met with the hatchet, concluding "if ever we are constrained to lift the hatchet against any tribe, we will never lay it down until that tribe is exterminated, or is driven beyond the Mississippi." This sentiment became manifest in forced removals across the continent. If invading settlers could not exploit the indigenous labor for their own purposes, they pressured them to leave areas so that European-Americans could get on with immigration and resource extraction. The complete subjugation through forced marches became a highly effective means of removal.

During the fall of 1862, Jefferson's sentiments were echoed by Minnesota Governor Alexander Ramsey, who stated, "The Sioux Indians of Minnesota must be exterminated or driven forever beyond the borders of the State." Unlike the Tsalagi, no segment of the Dakota population signed a treaty agreeing to its removal. Instead, the U.S. government considered the forced removal of Dakota people from their homeland to be a justifiable consequence of the U.S.–Dakota War of 1862. Rather than viewing warfare as a reasonable course of Dakota action in light of repeated U.S. violation of treaty obligations, the United States instead unilaterally abrogated Dakota–U.S. treaties and decided to take the remaining Dakota lands for European-American immigration.

The Dakota were removed from their Minnesota homeland in two successive waves. Women and children were force marched on a seven-day, 150-mile journey to Fort Snelling in St. Paul, where they spent the winter of 1862–1863. Forming a four-mile-long procession as they walked, an unknown number of the 1,700 women and children died along the way, many from the brutality of soldiers and citizenry who attacked them along the way as they were paraded through European-American towns. The following spring, the remaining thirteen hundred were sent down the Mississippi River on boats to St. Louis and then up the Missouri River to the Crow Creek Reservation in South Dakota. Three hundred and three Dakota men were tried and convicted of war crimes at the end of the war. While they awaited execution orders from Abraham Lincoln, they were shackled and placed in wagons that took them to a concentration camp at Mankato, Minnesota. After thirty-eight were hanged in the largest mass execution in U.S. history on December 26, 1862, the rest were sent down the Mississippi the following spring where they were imprisoned in Davenport, Iowa, for three years. After these forced removals were accomplished, Dakota lands were cleared for unimpeded immigration.

The Dine (Navajo) in the Southwest faced a similar forced march and removal in the 1864 Long Walk. As European-American immigration increased in the area and conflicts arose, Christopher Houston "Kit" Carson was sent to demonstrate that "wild Indians could be tamed." He implemented a brutal policy that included the destruction of crops and livestock, pillaging the land, and killing of the Dine. These scorched-earth tactics were meant to hurt not just the warriors of the nation, but also the noncombatants, the women and children, by forcing them into starvation and submission. Once the Dine were gathered at Fort Defiance, Arizona, they were force marched three hundred miles to Fort Sumner in the Bosque Redondo (in New Mexico Territory). The Dine named their concentration camp Hweeldi, the Place of Despair. Suffering starvation, disease, and harsh weather conditions with grossly inadequate clothing and shelter, at Hweeldi the Dine lost approximately thirty-five hundred out of their population of nine thousand. Unlike most indigenous peoples, however, the Dine were allowed to return to their homeland in 1868, where they continue to maintain the largest indigenous land base in the United States.

Forced marches were simply a means to an end. They allowed for large numbers of indigenous peoples to be transferred from one location to another, usually from their homeland to sites farther west, while their homelands were opened for nonindigenous settlement. Few indigenous peoples have ever recovered from the trauma caused by the disconnection from homeland and the accompanying destruction of their way of life. While the initial and significant loss of life caused from forced marches was enough to wreak havoc with any population, the devastation is compounded for indigenous peoples because of the simultaneous loss of land and way of life. Stories of suffering, particularly of the women and children, remain painful episodes in indigenous American history.