Nowadays, the extensive use of e-learning in higher educational institutions in many countries leads us to apprehend the reality, precisely the key success/failure factors of the implementation, of e-learning systems in these institutions. This motivation becomes more and more important, inevitable, and urgent, especially for institutions that have heavily adopted e-learning systems under exceptional conditions without any prior planning, such as the COVID-19 pandemic. From this perspective, this research aimed to provide an e-learning success model in the context of the COVID-19 pandemic by assessing e-learning effectiveness and by investigating the key antecedents of e-learning effectiveness. The literature review led to the identification of four main factors influencing e-learning effectiveness: The e-learning system, e-learning readiness, interactivity, and resistance to change. These four variables constituted the antecedents of an effective e-learning system, which was tested in a KSA context. A structured survey, including a sample of 1202 students from Imam Mohammad Ibn Saud Islamic University was used to examine the linkages among our proposed model. The model, with a total of ten direct and six indirect relationships, was tested by using structural equation modeling. The research findings indicate that effective e-learning is supported by the interactions between four factors: the e-learning system, e-learning readiness, interactivity, and resistance to change.