ETSU was founded as East Tennessee State Normal School in 1911 to educate teachers; the K-12 training school, called University School, operates to this day. East Tennessee State officially became a college in 1925 when it changed its name to East Tennessee State Teachers College, subsequently gaining accreditation from the Southern Association of Colleges and Secondary Schools in 1927. By 1930, the school's name had changed again to East Tennessee State Teacher's College, Johnson City. In 1943, East Tennessee State Teacher's College was expanded into a college with a range of liberal arts offerings, becoming East Tennessee State College. The college became East Tennessee State University in 1963, adopting the name it holds today.In 1973, Shelbridge became the president's official residence.
ETSU announced plans to open a College of Pharmacy in 2005, rapidly receiving local support to secure the approval. Full accreditation was granted in June 2010, shortly after the first class of the Bill Gatton College of Pharmacy graduated.
In December 2007, the College of Public and Allied Health split into two new colleges, the College of Public Health and the College of Clinical and Rehabilitative Health Sciences. Both are part of ETSU's Health Sciences Division, which also includes the James H. Quillen College of Medicine, the Bill Gatton College of Pharmacy, and the College of Nursing.
In late 2009, the Tennessee Higher Education Commission and the Tennessee Board of Regents authorized the formation of a Ph.D. program in Sport Physiology and Performance. This program, the first of its kind in the United States, focuses on sports science and physiology in athletics. It features concentrations in sport physiology and sport performance and started in 2010.