Music courses were first offered at the University of Kentucky (then known as the Agricultural and Mechanical College of Kentucky) in 1881. The Department of Music was established decades later, in 1918, and received its first national accreditation in 1937. Over the next few decades the Department added graduate degree programs, dedicated a new building on north campus, and became a School. With its growing success, advocates of the School formed the Friends of the UK School of Music in 1991 to provide public support. Five years later the UK Opera Theatre program was established and two years after that the John Jacob Niles Center for American Music.

In the 21st century, three directors have presided over the School. The School's ensembles have enjoyed tremendous opportunities to perform with extraordinary musicians in extraordinary locations. The UK Symphony Orchestra has performed with Arlo Guthrie, Lang Lang, Itzhak Perlman, Natasha Peremkski, and more. They performed with the Boston Pops in Rupp Arena in 2010 for Keeneland's 75th anniversary celebration. The UK Choirs have traveled to Spain, Italy, England, Ireland, and France. The UK Wind Ensemble took a 10-day tour to China in 2008. UK Opera Theatre performed "Our Lincoln" at the Kennedy Center in 2009. The UK Jazz Ensemble made its first European tour in 2011 with appearances at the Montreux Jazz Festival and the North Sea Jazz Festival. Three years later it toured China.

In 2013 the School joined with other units from the College of Fine Arts for the Living Landscapes Festival on UK’s campus, collaborating with students and faculty from the Art College of Inner Mongolia University (IMU), part of an exchange with the University. Students in UK Symphony Orchestra, Percussion Ensemble, Improvisation and Jazz Ensemble performed side-by-side with students from IMU. Additionally, a variety of master classes were held with IMU faculty and students. Two years later, in 2015, representatives from the School traveled to Inner Mongolia to collaborate with the University once again on performances, master classes, and workshops.