Cherokee is located in the southern part of San Saba County, almost mid-way between San Saba and Llano on Highway 16. In the late 1850s, the settlement was referred to as Cherokee because of its proximity to the Cherokee Creek which still flows through the area today. The State Handbook of Texas states "P. P. "Pop" Woodard established a ranch five miles west of the site of what is now Cherokee." The 1860 San Saba County Census lists a number of people as having Cherokee as their Post Office.

Francis Marion Behrns established the Cherokee Academy around 1894. It was called the West Texas Normal and Business College (1896) and later Cherokee Junior College (1911). The county school district purchased the building in 1921 and it was used for Cherokee High School until fire destroyed it in 1945. The school was rebuilt using its original façade.

Some sources with information about Cherokee include:

Goldie Smith Conley, Cherokee Creek Country: A History (Austin: Nortex Press, 1988).

Alma Ward Hamrick, The Call of the San Saba: A History of San Saba County (San Antonio: Naylor, 1941; 2d ed., Austin: Jenkins, 1969).

San Saba County History (San Saba, Texas: San Saba County Historical Commission, 1983).

Alice Gray Upchurch, "A Sketch History of San Saba County," Southwestern Historical Quarterly 50 (July 1946).

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