The first schoolhouse within Louisville was a one-room log cabin located on the corner of Nickelplate and Main Streets.

In 1872, Louisville's seat of learning was moved again to another two-room brick building, located upon South Chapel Street.

[2] In 1924, Louisville High School again moved to a much larger campus, which included ten classrooms, an auditorium, a gymnasium, and a library.

[3] The construction of Louisville High School's present campus commenced in 1964, and the new building opened in 1967.

Louisville was a 2008 Bronze Medal Winner of America's Best High Schools, given by the U.S. News & World Report.

This includes an unbeaten streak of 38 games, which is still the fourteenth-longest in Ohio high school football history.

[8] These teams were led by head coaches Gaylord ("Hap") Lillick from 1962–1964 and Paul Starkey from 1965–1966.

In 1989, Louisville High School decided to leave the Federal League for the newly-formed Northeastern Buckeye Conference.

For many years, the two teams met during the tenth, and final, week of the OHSAA football regular season.