The hospital has the largest single-floor critical care unit in the world with 100 beds, and is the home of the Royal Centre for Defence Medicine for military personnel injured in conflict zones.

One of these, Queens Hospital, established in 1840 by a young local surgeon William Sands Cox, was predominantly for clinical instruction for the medical students of Birmingham.

In 1884 these institutions, including Cox's medical school, united as part of Mason College, which later became the University of Birmingham.

[10] The new hospital was procured under a Private Finance Initiative contract with Consort Healthcare signed in early 2006.

[11] The hospital was designed by BDP Architects and construction, which was undertaken by Balfour Beatty[11] at a cost of £545 million, began in June 2006.

[13] A sky-bridge was erected between one of the towers and the retained estate allowing access to the departments of oncology, the pharmacy and the Wellcome Research Centre.

[21] Defence personnel are fully integrated with the NHS staff at the hospital, and they treat both military and civilian patients.

The RCDM has links with the University of Birmingham Medical School, and with Birmingham City University (where the Defence School of Health Care Studies is based, which provides training for military nurses and other health professionals).

[29] As of October 2021 the Care Quality Commission rated the Queen Elizabeth Hospital overall as "requires improvement".