The Anderson County Museum is situated on the former site of Anderson Girls High School. The original structure, an imposing multi-story brick building, was built in 1918. At that time, both boys and girls attended the school known as Anderson High School. In 1921, a fire swept through the building requiring extensive repairs. In 1923, the school administration decided to split the student body along gender lines. Girls attended the newly named Anderson Girls High School, and the boys attended Anderson Boys High School, which was located at the corner of Broyles and South McDuffie Street.
In 1961-1962, the student body from Girls High School moved to their new school (T.L. Hanna) on Greenville Highway. The former Girls High School structure would be used for many educational purposes but eventually deterioration caused it to be demolished in 1970. In 1971, the new Anderson County Library was built on the site. In May 2003, the newly renovated library building opened its doors as the Anderson County Museum.