The hospital was founded near 11th and Wazee, but in 1873, a new medical center was built at the corner of 6th Avenue and Cherokee; this is where Denver Health Main Campus is located to this day.

[2] The hospital was well known for founding the first nursing school west of the Mississippi and for being one of the earliest facilities for treating Tuberculosis.

[2][10] The Authority was created by the Colorado General Assembly in 1994 as a political subdivision of the state.

Through grant-funded programs, Denver Public Health conducts research on infectious diseases, including hepatitis surveillance; tuberculosis clinical trials; HIV/AIDS prevention, counseling, testing and treatment; and vaccine trials.

The Denver Department of Environmental Health, a Denver government agency, manages and oversees the operating agreement to contract with Denver Health to provide services related to the medical investigations and medical services for disease control (including clinics) and the administration of vital birth and death records.