It has been reported but still not verified why COVID-19 infection transmitted differentially across societies. This paper intends to investigate the association of cultural orientation to the differential spread of present pandemic. Initially, Ordinary Least Squares estimation and subsequently, a Two-Stage Least Squares analysis with Index of Historical Prevalence of Diseases as an Instrumental Variable is used to claim the findings. This study suggests that countries with higher individualistic values have significantly higher COVID-19 infections and vice-versa. The results are robust even after controlling for a number of related confounding factors such as density of population, percentage of urban population, uncertainty avoidance index, government effectiveness, political stability, voice and accountability, and rule of law. The results indicate human behavior is responsible for the differential spreading of COVID-19 infections across countries and hence provide a rationale to social distancing, government’s interventions and adherence to group norms for containment of this pandemic.