Despite the prevalence of mental health problems, society continues to stigmatize and discriminate against people with mental illness and in particular, schizophrenia. Among the negative consequences of stigma, is that some individuals with mental illness internalize negative stereotypes about themselves, referred to as self-stigma, which is associated with a reluctance to seek needed treatment. The challenge to overcome mental illness stigma has led to the development of global anti-stigma initiatives, which effectively engage young people in school-based programs. The present study examines the effectiveness of a single-session anti-stigma intervention with high school youth (n = 254). The findings replicate and extend previous work demonstrating that a brief anti-stigma initiative can produce significant improvements in knowledge, social distance, and self-stigma. Self-stigma was found to be associated with low self-esteem and factors affecting self-disclosure were identified. Implications for school curricula, mental health policy, and future research are discussed. (Contains 1 table.)