On September 11, 1922, South Side High School opened its doors to students for the first time.

When South Side High School first opened, desks and other furnishings had not been delivered to classrooms.

At the time South Side opened, it was the largest one-story school building in the United States.

In 1982, South Side was elected to permanent membership in the College Board – one of only thirteen Indiana high schools at that time to be so honored.

Seven principals have served the school in the past: Robert Harris, 1922–1926; R. Nelson Snider, 1926–1963; Jack E. Weicker, 1963–1990; Jennifer Manth, 1990–2001; Thomas Smith, 2001-2010; Carlton Mable, 2010-2018; and Adam Swinford, 2018-2022.

[4] Ninety-five individual staff members have served the school for twenty-five years or longer.