The original hospital opened on May 19, 1894, in a wooden building on a 17-acre (6.9 ha) meadow located at Oak Lawn and Maple avenues.

[6] The new Parkland tower blocks were redeveloped in 1981, and the triangular wing at the hospital's entrance on Harry Hines Boulevard opened in the late 1980s.

[10] Two days after the assassination, November 24, Oswald was rushed to Parkland after being shot in the abdomen by Ruby and died in operating room #5 after over ninety minutes of surgery.

A plaque there marked the location where Trauma Room 1 was previously in the prior Parkland,[13] and then became a corridor in the hospital's radiology department.

[14] Parkland's JFK history is noted on a wall at the new hospital[15] and at the John F. Kennedy Park for Hope, Healing and Heroes memorial on campus.

Parkland earned top marks in meeting non-discrimination and training criteria that demonstrate its commitment to equitable, inclusive care for LGBT patients and their families.

[30] In addition, the campus has six LEED Gold certified buildings, the first of which was awarded in 2013, that employ water reclamation, solar energy, and native landscaping.

[31] Parkland is also the second largest adopter of renewable energy in the Texas healthcare sector, earning the hospital recognition in the Environmental Protection Agency's Green Power Partnership.

[33] In May 2017, Fred Cerise, MD, MPH, president and CEO of Parkland Health & Hospital System was appointed by the U.S. Comptroller General to the Medicaid and CHIP Payment and Access Commission (MACPAC).

[34] In 2016, the staff of Parkland's Rees-Jones Trauma Center began an initiative to teach classes to the community members so that they can learn how to recognize life-threatening bleeding and administer appropriate medical treatment before professional rescuers arrive.

Parkland "Stop the Bleed" classes have been adapted from courses including the U.S. Military's Tactical combat Casualty Care Guidelines and the Prehospital Trauma Life Support (PHTLS) course and a part of a large U.S. Government effort to make "Stop the Bleed" training the CPR of the 21st century.

[35] The staff of Parkland Memorial Hospital's Emergency Department and Rees-Jones Trauma Center received the 2016 Texas Preparedness Leadership Award for "Outstanding Service in Response to the 2016 Dallas Police Shootings."

[45] In May, 2014, a new 44,300-square-foot, Parkland Health & Hospital System-affiliated outpatient clinic near Fair Park began construction on a 7-acre site adjacent to DART's Hatcher Station.

Exam rooms feature flexible equipment setups, and an on-site conference facility accommodates education and wellness programs.