The objective of this research is to investigate how cultural differences affect consumers’ online purchase behavior. We reviewed the recent literature on cross-cultural studies on online behavior and building on Hofstede’s theory of cultural dimensions and the theory of planned behavior (TPB), we developed a conceptual model exploring how the dimensions of national culture influence perceptions of website usability, trust, and perceived risk, which in turn impact on intention to use and online purchase behavior. A web-based questionnaire was distributed to a sample of 350 European and Asian consumers actively using Alibaba e-commerce platforms. The conceptual model was validated through a confirmatory factor analysis (CFA), while structural equation modelling (SEM) was used to empirically test the hypothesized relationships among variables. Results showed how culture significantly influenced website usability and perceived risk in European consumers and, in turn, their intention and behavior. Differently, culture significantly influenced trust of Asian consumers, as well as their intention and online behavior. With this study, we contribute to the literature on consumer online purchase behavior from a cross-cultural perspective. As culture emerged among the significant antecedents of mechanisms explaining online purchase behavior, e-tailers should tailor digital marketing strategies according to consumer cultural differences.