The past several decades of e-learning empirical research have advanced our understanding of the effective management of critical success factors (CSFs) of e-learning. Meanwhile, the proliferation of measures of dependent and independent variables has been overelaborated. We argue that a significant reduction in dependent and independent variables and their measures is necessary for building an e-learning success model, and such a model should incorporate the interdependent (not independent) process nature of e-learning success. We applied structural equation modeling to empirically validate a comprehensive model of e-learning success at the university level. Our research advances existing literature on CSFs of e-learning and provides a basis for comparing existing research results as well as guiding future empirical research to build robust e-learning theories. A total of 372 valid unduplicated responses from students who have completed at least one online course at a university in the Midwestern United States were used to examine the structural model. Findings indicated that the e-learning success model satisfactorily explains and predicts the interdependency of six CSFs of e-learning systems (course design quality, instructor, motivation, student-student dialog, student-instructor dialog, and self-regulated learning) and perceived learning outcomes.