Oglethorpe County High School was preceded by the Meson Academy, which opened in Lexington in 1806[4] and ran as an academy for school children with separate male and female departments[5] until its closure in 1918.

[6] After the academy's closure a local group called the Lexington Woman's Club which had formed in 1916, lobbied for the creation of a new school in its place.

Because of their efforts, the Meson Academy was reopened as Oglethorpe County High School in 1924–1925.

[11] The school started a joint program with the University of Georgia's College of Education in the late 1980s called OH-STAY (short for Oglethorpe High STAY) to try to tackle the school's high dropout rate.

The program used a $55,000 grant from the Metropolitan Life Foundation to pay for a student advocate who helped keep students in school and provided tutoring, while also training teachers to look for signs of and preemptively address potential dropouts.