As part of its mandate to collect materials related to American history, the Manuscript Division is home to thousands of collections. Over a hundred of these touch significantly on the histories and cultures of Native Americans. For the purposes of this guide, "Native Americans" refers to Indigenous peoples from the lands of the contemporary United States. The U.S. borders with Mexico and Canada split many Native communities in two, and some collections feature Native peoples who moved, maintained relationships and trade, and shared culture and tribal authority across these borders.

The division's collections cover topics like Native languages, Indian wars, settler colonial education, sovereign nation diplomacy, and U.S. presidential and governmental agency Indian policies. They include material relating to Native communities from Florida to Alaska and the regions in between. Larger Native nations such as the Cherokee and Lakota are particularly well-represented, but over 150 Native groups are listed in the community name index in this guide.

The materials in these collections come almost exclusively from Euro-American men, though materials created by Native people are highlighted throughout this guide. Materials created or collected by non-Native people can be very valuable to researchers interested in how Euro-Americans interacted with Native individuals and communities. Other materials reflect Native voices, Native visual art, and Native participation in the collection of linguistic and folkloric documentation. Researchers are encouraged to think critically about the acquisition and content of the Library's collections.

The collections described in this guide are historical, but Native Americans are not just a part of the past. They have been living in the lands now defined as the United States since time immemorial. And despite centuries of war, displacement, and violence, Native American cultural expression, traditions, and practices have flourished. The Library of Congress, situated near the confluence of the Potomac and Anacostia rivers, stands on the land of the Nacotchtank (Anacostan), Piscataway Conoy, Pamunkey and Manahoac nations.