For 57 years, the Kluge Children's Rehabilitation Center (KCRC) provided the region with a wide range of children's rehabilitation and developmental services. As the center attained international acclaim, it began to receive patients from around the world. The establishment of the center reaches back to the 1950s when the University of Virginia (UVA) Department of Orthopedics recognized a need for a children's treatment facility. Through the efforts of the Department of Orthopedics, funds were raised to build a new center, known as the UVA Rehabilitation Center for Handicapped Children, which opened in November 1957. The center was constructed on the site of the former Rucker Home for Children, an institution established in 1941 for young patients with tuberculosis of the spine. When the Rucker Home, named for its initial benefactor, William J. Rucker, was demolished to make way for the new center, stones from the original house were used to build a wall that bordered the front of the KCRC property along Ivy Road. An orthopedic surgeon at UVA, Dr. Hamilton Allen, became the center's first director upon its opening in 1957. Some time later, the name of the center was changed to the Children's Rehabilitation Center (CRC), and in 1965 the center became a formal part of the UVA Hospital system.

The facility was renovated in the early 1970s when an education wing, pool, and gymnasium were constructed. Additional improvements were to follow, and after a $2.5 million donation from John and Patricia Kluge, the center was rededicated as the Kluge Children's Rehabilitation Center (KCRC) in 1988. A second expansion completed in 1989 included a designated outpatient services area. In the late 1980s, with its updated facilities and under the leadership of Medical Director Dr. Sharon Hostler, KCRC adopted a stronger focus on research and clinical training.

During its 57 years in operation, KCRC's inpatient care treated thousands of children with brain and spine injuries, chronic lung conditions, and serious feeding issues. KCRC's diverse outpatient services included developmental pediatrics, pediatric orthopedics, and a wide range of disability-specific clinics for diabetes, down syndrome, cerebral palsy, cystic fibrosis, physical and occupational therapy, dentistry, autism, nutrition, and much more. Over the years, KCRC's focus on family-centered care brought it national attention and tremendous success.

In 2012 KCRC stopped receiving new patients in preparation for the relocation of pediatric services at UVA from the KCRC building on Ivy Road to the Children's Hospital in the Battle Building on West Main Street, adjacent to the main UVA hospital. The move was completed in July 2014. In the new facility, the pediatric care center was renamed the UVA Child Development and Rehabilitation Center.