The hospital opened on September 27, 1972, by 19 physicians from the community to serve the area's swiftly increasing population.

[4] The Cardiac Rehab Center, which cares for heart attack victims and people with coronary artery disease, opened in 1980.

[4] Healthcare workers picketed at the hospital in October 2022, protesting against low wages and understaffing.

[6] On February 1, 2024, UCI Health, part of the University of California, Irvine, agreed to purchase Placentia-Linda Hospital from Tenet Healthcare.

[13] From 2009 to 2011, Yashwant Balgiri Giri, an anesthesiologist who worked at the hospital, sexually assaulted three female patients while they were under anesthesia.