The museum contains 40 panels that illustrate local Cherokee history through photographs and drawings. This allows visitors to connect to the history of the area through visual depictions. In addition to the Cherokee history on display, the museum contains artifacts from early pioneer settlers. Many hand-made household items and farming tools are displayed, maintaining the history of some of the earliest settlers in the area.
The Cherokee County Historical Museum is part of the Trail of Tears National Historic Trail. This trail commemorates the Cherokee and other tribes who were forced to move to Oklahoma on the Trail of Tears. The museum houses a replica of the houses Cherokee residents used before their removal, log cabins that were typically used by settlers after the Cherokee were removed.