Land for the Cleveland Public School District's new commercial high school was originally acquired in 1907 along East 107th Street in University Circle. However, disputes and discussions about the nature and design of the new high school in the Cleveland district would ensue for nearly twenty years. By 1926 a Cleveland Press clipping illustrated a labeled photograph of the district property along East 107th Street. Cathedral Latin School and the Normal School are labeled bordering the proposed placement of the new John Hay High School. A Cleveland Plain Dealer article of September 14, 1929 cited the new school opening and dedication at that time. Taking its name from a great American statesman and Cleveland native, John Hay High School was like the school's predecessor, Longwood Commerce High School, focused on business training.
The school was ultimately created as a commercial school providing courses related to commerce, business, and office skills. As a result, enrollment at John Hay was predominantly female for many years to come and enjoyed much success graduating skilled office workers ready for employment. A May 14, 1954 article in the Cleveland Press was headlined "Men-Wanted Sign Out for 25 Years" and cited an 85% female graduate rate since the school's opening in 1929. A gradual redesign of John Hay's curriculum provided for a more comprehensive course of study that began to attract male students during the late 1950s and 1960s. The 'Bookeepers' changed to the 'Hornets' as male and female athletic programs were likewise designed to accommodate students seeking comprehensive studies and activities.
John Hay's reputation would change in time. With its transition to a comprehensive school, new challenges faced the administration, faculty, and students, not dissimilar to other schools in the district facing urban issues of racial and economic discord during the 1960s. The school became the site of student protests, lockouts, and other challenges in the next three decades. Disruptive students were responsible for a fire in the school in January, 1968 resulting in 32 student suspensions. In November, 1968, students conducted a "wildcat strike" and held an assembly to protest a new discipline policy being imposed at the school. Several other items were on their agenda including lavatory conditions, cancellation of social events, classroom equipment complaints, and building access concerns. A cafeteria fight ensued the next day as school closed for the Thanksgiving holiday. By January, 1969 parents, students, teachers, and administrators were disputing problems at the school alleging drug trafficking, intoxicated teachers, and neighborhood influences. By February, more unrest was brewing as students called for 'Black Unity'. At the end of February and into March, John Hay was closed for more than six school days following student protests and grievances with the school district. Grievances were resolved and an orderly re-opening of the school ensued on March 6.
Throughout the 1970s and 1980s as the Cleveland Schools worked to implement a federal desegregation order, John Hay remained a center of action and protest within the district. John Hay was temporarily closed in 2008-09 for remodeling. It has since reopened and currently serves students as a thematic health care education facility as a partner with the Cleveland Clinic.