Covering a period from approximately 1779 to 1850, this dissertation studies natural resources and land use in Cherokee country before and after forced Cherokee removal from east of the Mississippi. As the market economy in the South grew in the late eighteenth and early nineteenth centuries, Euro-Americans perceived the Cherokee Nation as an obstacle to commercial transportation and economic expansion. Southern leaders such as John C. Calhoun and Wilson Lumpkin planned to build canals and railroads through the Cherokee Nation. Disputes over saltpeter, gold, salt, and iron mining rights and the ownership of ferries, taverns, and turnpikes caused conflict. The Cherokees resisted all forms of encroachment on their natural resources and continuously modified their laws and methods of dealing with intruders. This dissertation examines the importance of the spread of cotton agriculture across the South, the availability of timber for establishing homesteads and small industry, and the medicinal herbs trade as factors in Cherokee land cessions. It also studies the extent to which a growing national interest in science, a national push for internal improvements, and the policies of the Corps of Engineers influenced Cherokee removal.