It is named for Henry W. Grady, an Atlanta Constitution journalist and later owner who became a major force in Georgia politics and advocated for a public city hospital.

The second Grady Hospital (at Butler Hall) opened in 1912 and was for whites only, with blacks being segregated at the Atlanta Medical College.

Even though it is a single building, and the two sides are connected by a hallway (Wing E), the facility was referred to in the plural ("The Gradys") during the years of segregation.

In February 2013, it was announced that Grady's net profit was $20 million and that 200-300 jobs had been added at the hospital in the preceding 18 months.

The Downtown Connector (Interstate 75/85) makes a large bend around the hospital on its otherwise due north–south route, dubbed the "Grady Curve" on traffic reports.

[12] On August 11, 1949, Gone with the Wind author Margaret Mitchell was hit by a speeding car while crossing Peachtree Street with her husband on the way to a movie.

The driver, who had 23 prior traffic violations, was thought to be drunk and was convicted of involuntary manslaughter and served an 11-month jail term.

Grady Hospital gained national attention for treating supermodel Niki Taylor after her near-fatal car accident on April 29, 2001, in which she suffered severe liver trauma.

Several press conferences were held outside the hospital discussing the gravity of her injuries and her slow recovery following more than 50 surgeries.

In AMC's The Walking Dead, Grady Memorial became a major setting for several episodes of the show's fifth season in 2014.