Glenville High School opened in 1892 on Parkwood Drive in Cleveland's east side village of Glenville. The student body grew so rapidly that even a series of early additions soon proved incapable of holding it, so a new Glenville High School building opened in 1904. Two years later, after Cleveland's annexation of the village, Glenville joined the Cleveland Metropolitan School District. Following years of migration from the Woodland neighborhood to Glenville in the early twentieth century, the red-brick two-story school reached a 90 percent Jewish student body. As the neighborhood grew and African Americans began migrating to Glenville for jobs and housing, the demographic changed to 90 percent African American by 1950. Additions were constructed in 1911, 1922, and 1939 to serve the growing enrollment, but the school found itself overcrowded by the 1950s and early '60s. In 1963, the school was well over its 1,608-student capacity with enrollment exceeding 1,900 students. To alleviate the problem, some Glenville residents were sent to nearby John Hay High School in Fairfax.
In 1963, Cleveland citizens voted to allow the Cleveland Metropolitan School District to receive a $55 million bond, from which $3.5 million went to build a new Glenville High School, since the present school at the time was old, small, and outdated (with its old science laboratories and equipment). The new Glenville High School opened for the new school year of 1966, located at its present day location of 650 East 113th Street. While the old school had one-way hallways, shared classrooms, and wooden floors, the spacious new school had large lecture halls, updated equipment, and a large gymnasium. Glenville High School had striking similarities to John F. Kennedy High School in the Lee-Harvard neighborhood. J.F.K. was built a year earlier, and as some Glenville alumni noted, the only difference from Glenville High School was that the blueprint was flipped, where the location of J.F.K. cafeteria was on the opposite side in Glenville High School. Glenville High School maintained a rivalry with J.F.K. High School in sports, as well as neighboring Collinwood High School. Glenville at the time was known for its track-and-field team, the Glenville Tarblooders. A "tarblooder" was a robot man, named after the men who "bled tar" from working on the railroads in the early 1900s.
Glenville High School has had notable alumni, whether it be athletes from Glenville's successful football team, politicians such as former Cleveland mayor Michael R. White and Howard Metzenbaum, actors like Steve Harvey and Ron O'Neal of Superfly fame, and the creators of Superman. In addition to its alumni, the school prides itself on its athletics, especially the track and football teams.