Mental illness is a global public health crisis. Although rates of untreated cases stand as a primary problem, stigma is a significant obstacle. Yet, global differences in levels and roots of stigma remain poorly understood. Using the Stigma in Global Context–Mental Health Study (SGC-MHS) data, we analyzed data on two components of stigma—prejudice and discriminatory potential—attached to clinically diagnostic cases of depression and schizophrenia. We examined whether stigma was higher in the East than West. Furthermore, we hypothesized that the link between prejudice and discriminatory potential in the East was due, in part, to cultural differences in the attributions about mental illness. With SGC-MHS’ nationally representative vignette data from over 11,000 respondents in 11 relevant countries (four Eastern, seven Western), analyses replicated past research of higher levels of stigma and more moral attributions in Eastern countries, particularly for depression. Moreover, prejudice-related disclosure spillover concerns predicted discriminatory potential (social distance) in the East, but not the West; this was driven by a greater emphasis on moral attributions in the East. Finally, exploratory analyses found that Western respondents endorsed higher discrimination for minority (vs. majority) group members with mental illness. In Eastern countries, the same pattern emerged for schizophrenia, but the reverse occurred for depression—greater stigma for majority as compared with minority group members. Together, these findings suggest that cultural differences in the sources of prejudice and attributions about the etiology of mental illness contribute, at least in part, to global differences in the profile of stigma.