This paper explores the factors influencing social acceptance toward persons with schizophrenia by examining the effects of perceived dangerousness, having knowledge, and social instability and investigates these conditions in a cross-cultural comparison of Japan and Vietnam. Social distance scales and random sample survey questionnaires based on vignettes were used to reconstruct social acceptance in Japan (n = 488) and Ho Chi Minh City in Vietnam (n = 185). Structural equation modeling was applied to explore the relation between social acceptance, perceived dangerousness, beliefs in Western psychiatric treatments, contact with people with schizophrenia, and cohorts having grown up during the Vietnam War.In both countries, contact reduced the perceived dangerousness of persons with schizophrenia and increased their social acceptance. Beliefs in Western psychiatric treatments informed by education-based knowledge, however, intensified perceived dangerousness in Japan, but increased social acceptance in Vietnam. The effects of education-based knowledge emerge differently according to each society's mental health system history. The Vietnamese cohort born during the Vietnam War showed greater social acceptance than others, while no effects were observed in Japanese cohorts. Social instability seems to change social values and negative social attitudes related to schizophrenia.