J.C.M. Merrillat - a native of Bordeaux, France - arrived in 1851 as the first principal of the school's Blind Department. He took over as superintendent of both the Deaf and Blind departments the following year. His house, a few minutes from the school, was added to the National Register of Historic Places in 1982. The school was co-educational from the start, an unusual choice for 1839, but it admitted only white students. For more than a century Virginia maintained two parallel systems - this school for white students in Staunton, and a separate institution at Hampton for Black students. The two were not the same in size, funding, or facilities. The deficit was the point of segregated education in the South: separate was never equal.

The U.S. Department of Health, Education, and Welfare required Virginia to desegregate its deaf and blind schools in the early 1970s. The Commonwealth submitted a plan in 1974, and the federal government accepted it. In 1978 the state announced a $1.8 million capital improvement plan for the Hampton campus - an attempt to bring its physical facilities closer to those at Staunton. The Hampton school remained a separate institution focused increasingly on students with multiple disabilities; Staunton's school became the state's primary residential program for deaf and blind students. Federal law had compelled what the state had been able to delay for decades.

The Blind Department teaches Braille reading and writing, mobility and orientation, life and self-advocacy skills, and a full academic curriculum. Technology has reshaped much of what is possible - screen readers, refreshable Braille displays, audio textbooks - but the foundational skills the school built around in the 19th century remain essential. The Deaf Department offers academics from elementary through high school, along with vocational programs and community work placements. Sports thread through both departments. The Deaf teams, the Cardinals, compete in the Mason-Dixon Schools for the Deaf Athletic Association; they won the Mason-Dixon basketball tournament in 1959, 1964, and 1970, and went undefeated in football in 1939, 1954, and 1969. The Blind teams, the Chiefs, compete in the Eastern Athletic Association of the Blind in sports including goalball - a Paralympic sport designed for visually impaired athletes.

After the 1975 Education for All Handicapped Children Act (later renamed the Individuals with Disabilities Education Act), local districts were required to educate students with disabilities in their own boundaries when possible. Enrollment at state schools like VSDB shifted as students with milder disabilities increasingly stayed in their home districts; by 1983 enrollment had dropped to about 300, down from 550 in the late 1960s. The school's mission narrowed to serving students whose needs are difficult to meet locally - children for whom a community of peers who sign or who navigate the world without sight makes a fundamental difference. In 2009, the General Assembly made VSDB independent of the Virginia Department of Education, with its own board of visitors. The 73-acre campus carries 28 buildings, most from the 1800s. Many alumni return as teachers and staff. A quarterly alumni newsletter, the Little Acorn, has been published for decades.