The landmark event that involved the relocation of Native Americans during the 19th century was the Trail of Tears. This tragic chapter in U.S. history occurred in the 1830s, when thousands of Cherokee and other tribes were forcibly removed from their ancestral lands in the Southeastern United States to designated Indian Territory west of the Mississippi River. This policy was fueled by the demand for land and resources and resulted in significant suffering, including disease and death during the harsh journey. The Trail of Tears symbolizes the broader impacts of manifest destiny and colonial expansion on Indigenous peoples.