Agnews opened in 1888 as the California State Asylum for the Insane at Agnews, situated on farmland in what was then rural Santa Clara County. The facility was designed to house patients with mental illness in an era when institutional confinement was the primary approach to psychiatric care. By the time of the earthquake, Agnews held hundreds of patients in a sprawling campus of brick buildings. The main administration building, an imposing Victorian structure, had not been designed to withstand the kind of seismic forces that the San Andreas Fault would unleash. The building's collapse trapped patients in their wards, many unable to escape locked doors and barred windows.

After the earthquake, the state rebuilt Agnews with a new mission and new architecture. The replacement buildings were designed to be earthquake-resistant, spread across a campus of low-slung structures surrounded by open grounds. Over the following decades, the institution's purpose shifted from psychiatric hospital to developmental center, serving people with intellectual and developmental disabilities. By the mid-twentieth century, the facility had been renamed Agnews Developmental Center, reflecting changing attitudes toward the populations it served. At its peak, the center housed thousands of residents on its Santa Clara campus.

California's deinstitutionalization movement, which sought to move people with developmental disabilities from large institutions into community-based care, gradually reduced Agnews' population over several decades. The center finally closed in 2009, ending more than 120 years of operation. The campus was redeveloped, with portions becoming a city park and other sections being repurposed for commercial and residential use. Sun Microsystems, and later Oracle, occupied parts of the former campus. Today, little remains to suggest that the manicured grounds were once home to one of California's largest state institutions, a place where the 1906 earthquake wrote one of its most devastating and least remembered chapters.