Previous research has suggested that culture influences perception and attention. These studies have typically involved comparisons of Westerners with East Asians, motivated by assumed differences in the cultures’ self-concept or position on the individualism-collectivism spectrum. However, other potentially important sources of cultural variance have been neglected, such as differences in traffic directionality shaped by the urban spatial environment (i.e., left-hand vs. right-hand traffic). Thus, existing research may potentially place too much emphasis on self-concepts or the individualism-collectivism dimension in explaining observed cultural differences in cognition. The present study investigated spatial cognition using a Simon task and tested participants from four nations (Australia, China, Germany, and Malaysia) that differ in both cultural orientation (collectivistic vs. individualistic) and traffic directionality (left-hand vs. right-hand traffic). The task used two possible reference frames underlying the Simon effect: a body-centered one based on global stimulus position relative to the screen’s center versus an object-centered one based on local stimulus position relative to a context object. As expected, all groups showed a reliable Simon effect for both spatial reference frames. However, the global Simon effect was larger in participants from countries with left-hand traffic. In contrast, the local Simon effect was modulated by differences in cultural orientation, with larger effects in participants from collectivistic cultures. This pattern suggests that both sources of cultural variation, viz. cultural orientation and traffic directionality, contribute to differences in spatial cognition in distinct ways.