Narrowly defined, a manuscript is a unique, unpublished item found nowhere else. Such items include papyri, clay tablets, diaries, letters, ledgers, etc. In a broader definition, a manuscript can cover a wide range of material that includes meeting minutes, unpublished reports, business cards architectural drawings and ephemera. The common thread is that manuscripts contain primary source information. The items created are by the actual event participants. Many of these items can be found in the Cline Library Special Collections and Archives manuscript holdings.

The Library preserves and makes available more than 290 distinct and separate collections that primarily focus on the development of the Colorado Plateau. Areas of collection strength include the growth of Flagstaff, Colorado River History, Native Americans, tourism on the Plateau, Grand Canyon, ranching, lumbering and environmental issues.