For three decades, scholars have focused on generalized interpersonal trust as the key component of social capital and there is a wide consensus that trust in strangers is the prime indicator of people’s general trust in others. However, little work with a specific focus on trust in strangers has been conducted in a comparative multilevel framework. The few existing studies are inconclusive because of deficiencies in both conceptualization and test strategy. Filling this gap, this article examines the determinants of trust in strangers on the broadest country base ever used in the study of trust, drawing on global cross-cultural evidence from the fifth and sixth rounds of the World Values Surveys—the first international surveys to include a direct question on trust in strangers. Reaching beyond conventional wisdom about the sources of generalized trust, we demonstrate that human empowerment at the country level is a powerful moderator of well-known individual-level determinants of trust. Specifically, in countries with lagging human empowerment, institutional trust, trust in known people, and material satisfaction are the only individual-level characteristics that enhance trust in strangers. We also detect an unexpected negative effect of education where human empowerment is lagging. In sharp contrast, in countries with advanced human empowerment, a much broader set of individual-level characteristics increases trust in strangers. This set includes ethnic tolerance, membership in voluntary associations, social movement activity, emancipative values, subjective well-being, age, and education. These insights inform a multilevel theory of trust, showing that human empowerment operates as a contextual activator of individual trust promoters.