The Hospital was conceived in 1994 by the Akwa Ibom State Government as the Akwa Ibom State Specialist Hospital, later renamed Sani Abacha Specialist Hospital. Clinical services started in January 22, 1996. In 1997, it was taken over by the Federal Government and further renamed Federal Medical Centre, Uyo. Following the establishment of a College of Health Sciences at the Federal University of Uyo, a Memorandum of Understanding (MoU) was signed in March 2001, between the Federal Ministry of Health, University of Uyo and the Hospital, making it the University of Uyo Teaching Hospital. This was necessary in order to enable the students do their clinical training.

It is important to note that the instrument which accorded the Hospital the status of a full fledged Teaching Hospital was finally signed in January 28, 2008 by the President and Commander-in-Chief of the Armed Forces of the Federal Republic of Nigeria, Alhaji Umaru Musa Yar’Adua.