Knowing how to build and maintain consumer trust is crucial for e-commerce. Despite the number of empirical studies that have explored the factors that influence consumer trust, none of them considers the relative importance of different antecedents and how they interact to influence consumer trust. Therefore, based on the integrated Decision Making Trial and Evaluation Laboratory (DEMATEL) and Interpretive Structural Modeling (ISM) approaches, we establish a hierarchical structural model, which not only demonstrates the intensity of the relationships but also identifies the interdependence among the drivers of consumer trust in E-commerce. The findings confirm that propensity to trust is the most important determinant of consumer trust. The brand-related factors and platform-related factors are prominent in the process of building trust as they influence consumer trust indirectly through propensity to trust. Geographic location, demographic variables, and high security are identified as the root causes that affect consumer trust through other trust antecedents. Furthermore, the findings of this study offer valuable insights into an important element of e-commerce and provide a useful platform for future research. More represented samples and factors are encouraged for further research to ensure research fairness and minimize consumer distrust and uncertainty.