Established in 1856, Louisville Male is the oldest public high school west of the Alleghenies. A growing 19th century river city needed a place to prepare its men for leadership, and so in 1861, Male was designated "The University of Public Schools in Louisville". Until 1921, Male granted bachelor's degrees.

The first building to house Male was at Ninth and Chestnut Streets. When a larger facility was needed, the school moved to First and Chestnut in 1899. The third move was to the corner of Brook and Breckenridge Streets in 1915. In August 1991, the school opened its fourth and current campus at the old Durrett High School on Preston Highway, which doubled the physical size of the school.

Male became the first magnet/optional program in Jefferson County Public Schools in the 1970's when it was chosen as the Traditional High School. The district wished to create a structured learning environment which focused on learning fundamentals. A climate of high expectations and standards was created through the combined efforts of students, faculty, administration, and parents.