Cherokee High School was founded in 1925 as Cherokee Vocational High School as it was the first designated vocational school in Colbert County. The school provides both academic and general diplomas and has dropped the "Vocational" part of the name. The first graduating class consisted of 22 students.
The original high school building was located where the current gymnasium stands. As the school expanded, the old high school became the junior high school. That building burned on January 21, 1971.
Cherokee High School is a member of the Alabama High School Athletic Association Class 1A. The school colors are blue and gold. The school mascot is the "Indians".
