Charity Hospital quickly outgrew its original facility, and a second hospital was built at the edge of the colony on Basin Street in 1743. A third hospital was built nearby in 1785. It was renamed the San Carlos Hospital in honor of King Charles III, King of Spain, after New Orleans was ceded to Spain in 1763.
A fire destroyed this hospital in 1809. Without a building, a temporary hospital was established at the Cabildo for a month, then at the Jourdan residence in the Faubourg Marigny for six months, then the dilapidated De La Vergne plantation for 5 years while a fourth hospital was built. This new hospital was built at the edge of the city on Canal Street where The Roosevelt New Orleans Hotel is currently located. The hospital was completed in 1815, but this hospital was widely criticized as inadequate and underfunded.
A fifth hospital was built within Girod, Gravier, St. Mary, and Common Streets in the Faubourg St. Marie in 1832. During the yellow fever epidemic of 1858, 2727 patients were admitted and of them 1382 died of the disease. Total patient admission that year was 11,337, being 9135 males and 2202 females. This hospital came under the administration of the Sisters of Charity, who would run the hospital for the next century. Under their care, Charity Hospital, partnered with the Medical College of the University of Louisiana.
By the 20th century, the city of New Orleans was rapidly expanding, and the demand for indigent medical services again exceeded Charity Hospital capacity. A sixth hospital was built on Tulane Avenue in 1939. At the time it was the second largest hospital in the United States with 2,680 beds.
The building's cornerstone lists the Federal Emergency Administration of Public Works (later called the Public Works Administration) as the building authority. The architects were Weiss, Dreyfous & Seiferth, who were also responsible for the Louisiana State Capitol in Baton Rouge. The hospital features two stone bas-reliefs and a cast-aluminum screen called Louisiana at Work and Play, all by artist Enrique Alférez.
The LSU Health Sciences Center in New Orleans (LSUHSC-NO) was built adjacent to Charity Hospital in 1931 under the aegis of Louisiana Governor Huey Pierce Long. Serving one of the largest populations of uninsured citizens, Charity Hospital also boasted the #2 Level I Trauma Center in the nation, with the #1 rank belonging to Cook County Hospital in Chicago, Illinois.
In 1968, the hospital lost a malpractice case before the U.S. Supreme Court. In Louise Levy, Administratrix v. Louisiana through the Charity Hospital of Louisiana at New Orleans Board of Administrators, et al., the court ruled that a child born out of wedlock could not be prevented from suing on behalf of a deceased parent. The Louisiana Department of Health and Human Resources (DHH) took control of Charity Hospital in 1970. The hospital was transferred to the Louisiana Health Care Authority (LHCA) in 1991 and to the LSU System in 1997.
Like its sister hospital, University Hospital, Charity Hospital sustained severe flood damage during Hurricane Katrina. The evacuation of patients from the flooded hospital made national headlines. After the storm, a temporary clinic named the Spirit of Charity was established at the Convention Center. The temporary Spirit of Charity Clinic was later relocated to the New Orleans Centre building adjacent to the Superdome. In February 2007, a renovated University Hospital had taken over interim responsibilities of emergency care to the city which Charity originally provided. In August 2015, the LSU Health Sciences Center completed the new $1.1 billion medical center named University Medical Center New Orleans. The hospital consolidated the functions of both the already closed Charity Hospital and University Hospital.
The Foundation for Historical Louisiana, as charged in HCR 89 of the 2006 Louisiana Legislature, hired the internationally renowned architectural firm, RMJM Hillier examine and evaluate if the building was worth saving, renovating. RMJM Hillier determined the art deco building to be structurally sound—with its original design being architecturally exceptional and “ahead of its time.” Rehabilitation into a 21st-century, state-of-the-art facility would be the fastest, most cost-effective way to return quality healthcare and a teaching hospital to New Orleans. This idea was scrubbed in favor of using University Hospital as an interim hospital and building University Medical Center New Orleans and a new Southeast Louisiana Veterans Health Care System Medical Center in the adjacent neighborhood of lower Mid-City.
Charity Hospital was featured in the TLC documentary series, Code Blue. The series documented the lives of the hospital physicians and their patients. The episodes often illustrated the rate of violence in New Orleans by chronicling the high volume of patients who were treated in the emergency department with gunshot or stab wounds. Charity Hospital was also featured in two episodes of TLC's Trauma: Life in the ER, which focused on Charity's emergency room, the busiest emergency room in the United States at the time. Charity Hospital was also in an episode of NY Med, where a doctor reminisces of his time spent at the hospital before it closed down. Big Charity, a documentary film by Alexander John Glustrom tells the untold story behind the death of Charity Hospital and unveils the truth about one of the largest single payouts of federal disaster funds in state history.