Southeast Missouri Hospital College of Nursing and Health Sciences is owned by Southeast Missouri Hospital. The original Southeast Missouri Hospital School of Nursing opened in 1928 when the hospital opened. It focused on educating and training individuals for registered nursing. The school closed as a result of economic hardships during the Depression years. Plans to re-open the hospital based nursing program as a LPN to RN educational program began in 1990. The Missouri State Board of Nursing, in 1992, awarded accreditation as a diploma program.

The School of Nursing transitioned to the College of Nursing with approval being granted by the Missouri State Board of Nursing in 1995. In 1999, the College of Nursing expanded its educational offerings to individuals not having prior nursing education. In 2000, the name of the College was changed to Southeast Missouri Hospital College of Nursing and Health Sciences when the Surgical Technology program was opened. In 2001, a Radiologic Technology program was added to the College. The School of Medical Laboratory Science opened in 1999 under the Clinical Laboratory of Southeast Missouri Hospital. In 2006, the Medical Laboratory Science Program joined the College of Nursing and Health Sciences. The RN-BSN program, the Associate of Arts (Emphasis: Allied Health) program and the Clinical Laboratory Assistant program were added in 2015.

The College was awarded accreditation by the Higher Learning Commission of the North Central Association of Colleges and Schools in May 2005.