The John Howard Payne Papers consist of fourteen volumes (many disbound and boxed for conservation purposes) of material relating to American Indians, primarily the Cherokee, between 1794 and 1842 (bulk 1825-1842).

Collection includes correspondence, extensive notes and research, transcriptions, memoranda, unpublished works, and government publications and other printed items. The first six volumes have been edited and annotated into two books by a historian and two anthropologists at Western Carolina University, published by the University of Nebraska Press in 2010. The introductions in these books provide the content of this part of the collection, with information and background on John Howard Payne and his collecting preparations for his history of the Cherokee, as well as of Daniel S. Butrick, the missionary whose extensive research was passed to Payne to use for the project.

Volumes 1 and 2 contain the manuscripts Payne prepared for his history of the Cherokee (which he designated as "Cherokee Papers"). Volume 3 contains research and notes of miscellaneous information on Indian history and customs by Daniel S, Butrick included in letters to Payne. Volume 4 is primarily letters to John H. Payne, 1836-1837, many with information on Indian history and culture. Volume 5 consists of letters and documents pertaining to the Cherokee. Volume 6 contains letters and documents relating to Cherokee history copied and/or collected by Payne, 1838-1840. Volumes 7-14 contain miscellaneous material including correspondence, with further letters to Payne from Daniel Butrick and other missionaries, and from John Ross, leader of the Cherokees. Also letters of Charles Hicks, John Ridge, Evan Jones and others, and family letters of the Elizur Butler family. There are sketches and essays on Indian tribes such as the Creeks, the Sioux and the Delaware by Benjamin Hawkins, William Turner, and James P. Evans; historical and ethnological information on the American Indian, included in letters from Henry G. Clauder, William Byrd Powell and Gerard Troost; correspondence and notes concerning the Cherokee Tribal Council, John Ross and the U.S. government.