Cross-cultural differences in attitudes toward schizophrenia are suggested, while no studies have compared such attitudes between the United States and Japan. In our previous study in Japan (Hori et al., 2011), 197 subjects in the general population and 112 physicians (excluding psychiatrists) enrolled in a web-based survey using an Internet-based questionnaire format. Utilizing the identical web-based survey method in the United States, the present study enrolled 172 subjects in the general population and 45 physicians. Participants' attitudes toward schizophrenia were assessed with the English version of the 18-item questionnaire used in our previous Japanese survey. Using exploratory factor analysis, we identified four factors labeled “social distance,” “belief of dangerousness,” “underestimation of patients’ abilities,” and “skepticism regarding treatment.” The two-way multivariate analysis of covariance on the four factors, with country and occupation as the between-subject factors and with potentially confounding demographic variables as the covariates, revealed that the general population in the US scored significantly lower than the Japanese counterparts on the factors “social distance” and “skepticism regarding treatment” and higher on “underestimation of patients' abilities.” Our results suggest that culture may have an important role in shaping attitudes toward mental illness. Anti-stigma campaigns that target culture-specific biases are considered important.