Wolfson Children's Hospital is a nationally ranked, non-profit, pediatric acute care hospital located in Jacksonville, Florida. It has 281 beds and is the primary pediatric teaching affiliate of the University of Florida College of Medicine-Jacksonville and the Florida branch of the Mayo Clinic Alix School of Medicine. The hospital is a part of the Baptist Health system, and the only children's hospital in the system. It provides comprehensive pediatric specialties and subspecialties to pediatric patients throughout Jacksonville and the North Florida region, but also treats some adults that would be better treated under pediatric care. Wolfson Children's Hospital also features the only Florida Department of Health-designated pediatric trauma referral center in Jacksonville, Florida, and the only American College of Surgeons-verified, Level 1 pediatric trauma center in the region.

The hospital is situated on the St. Johns River waterfront in Downtown Jacksonville and is part of a large medical complex which also includes Baptist Medical Center Jacksonville, Baptist MD Anderson Cancer Center, and Nemours Children's Clinic.

In 1946, Morris David Wolfson wrote a letter to his sons, Sam Wolfson, Louis Wolfson, Saul Wolfson, Cecil Wolfson, and Nathan Wolfson asking them to build a children's facility in Jacksonville, Florida. A $500,000 donation from the Wolfson Family Foundation led to the establishment of Wolfson Children's Memorial Hospital, a 50-bed pediatric wing at Baptist Memorial Hospital (now Baptist Medical Center Jacksonville) in 1955.

The hospital grew incrementally during its early years, establishing a Cystic Fibrosis Center in 1963, a Children's Tumor Program in 1970 and an eight-bed Neonatal Intensive Care Unit in 1971. That same year, pediatricians with the Northeast Florida Pediatric Society signed an agreement stating that a consolidated center of excellence to be known as Jacksonville Children's Hospital would be the best way to serve the region's children and families. With the unveiling of a corporate charter in May 1971, Jacksonville Children's Hospital was incorporated as a pediatric inpatient facility within Wolfson Children's Memorial Hospital.

In April 1973, a 15-bed Pediatric Intensive Care Unit opened at Jacksonville Children's Hospital, increasing Wolfson Children's Memorial Hospital's bed capacity to 101. The hospital formed an auxiliary in June of that year, with volunteers serving throughout the facility and raising funds for special projects and facility expansion.

In 1976, Larry Freeman was appointed administrator of Jacksonville Children's Hospital. Ellen Cavert was elected chairman of the Women's Board of Jacksonville Children's Hospital with a mission to raise funds and awareness. In December 1977, the group held its inaugural Christmas antiques show to raise funds for the expansion of cancer treatment for children.

In 1980, Jacksonville Children's Hospital was renamed Jacksonville Wolfson Children's Hospital. A pediatric radiology department was established in 1981 in memory of founding hospital trustee J.W. Hayes, MD. The Pediatric Urgent Care Center, an extension of the Emergency Center at Baptist Medical Center, opened in October 1985.

In 1987, Wolfson and Nemours Children's Specialty Care, Jacksonville, began their affiliation to better serve the area's children. Wolfson also began an academic affiliation with the University of Florida College of Medicine-Jacksonville in the 1990s, training pediatric residents, fellows and other professionals in pediatric medicine. In 2019, they began training anesthesia residents from Kendall Regional Medical Center. It is also serves as a pediatrics training site for physicians in the Mayo Clinic College of Medicine.