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In 1831, the Cherokee, Chickasaw, Choctaw, Muscogee-Creek, and Seminole (sometimes collectively referred to as the Five Civilized Tribes) were living as autonomous nations in what would be called the American Deep South. The process of cultural transformation (proposed by George Washington and Henry Knox) was gaining momentum, especially among the Cherokee and Choctaw. Andrew Jackson continued and renewed the political and military effort for the removal of the Native Americans from these lands with the passage of the Indian Removal Act of 1830.

In 1831 the Choctaw were the first to be removed, and they became the model for all other removals. After the Choctaw, the Seminole were removed in 1832, the Creek in 1834, then the Chickasaw in 1837, and finally the Cherokee in 1838. After removal, some Native Americans remained in their ancient homelands - the Choctaw are found in Mississippi, the Seminole in Florida, the Creek in Alabama, and the Cherokee in North Carolina. A limited number of non-native Americans (including African-Americans - usually as slaves) also accompanied the Native American nations on the trek westward. By 1837, 46,000 Native Americans from these southeastern states had been removed from their homelands thereby opening 25 million acres (100,000 km2) for predominantly white settlement.

The fixed boundaries of these autonomous tribal nations, comprising large areas of the United States, were subject to continual cession and annexation prior to 1830, in part due to pressure from squatters and the threat of military force in the newly declared U.S. territories -- federally administered regions whose boundaries supervened upon the Native treaty claims. As these territories became U.S. states, state governments sought to dissolve the boundaries of the Indian nations within their borders, which were independent of state jurisdiction, and to expropriate the land therein. These pressures were magnified by U.S. population growth and the expansion of slavery in the South.