The purpose of this study was to estimate the effects of a theoretical model encompassing psychological theories underlying student retention in postsecondary education. New conceptual operationalizations were applied to elaborate Bean and Eaton’s theoretical model of student retention. The influences of student entry characteristics, environmental interactions, psychological processes, attitudes, and intentions toward persistence were assessed using a repeated measures, longitudinal design. Within the framework, persistence is an endogenous variable based on actual re-enrollment into subsequent semesters. Three student samples were drawn from a large urban research university in California. Survey data collected from a first-year seminar and the National Survey of Student Engagement (NSSE) and were used to test pathways of Bean and Eaton’s conceptual framework. The data were analyzed through Structural Equation Modeling (SEM) and moderated mediation considering the following dichotomized groups: male/female, underrepresented/nonunderrepresented students, first-generation/non-first-generation students. Analysis of first-time freshman cohort data revealed that the hypothesized model is supported across all three samples in 2018, 2019, and 2020. The results reveal that measures of locus of control, self-efficacy and coping were found to indirectly predict persistence into the second year and third year of college, while measures of academic interactions, academic integration, social integration, and institutional fit were directly predictive of persistence. Path level differences between first-generation students and non-first generation students were found in the 2019 cohort in the relationships between past behavior and faculty academic interactions, and normative beliefs and classroom interactions. None of the other grouping variables yielded moderating effects. The fit statistics for three models are within the acceptable range, with the 2020 SEM model producing the best fit. The 2018 model, which included NSSE independent variables and assessed persistence into the third year, had the most explanatory power. Across all three cohorts, both classroom and faculty academic interactions exerted the strongest indirect effects on persistence. The results from this study provide strong support for the indirect effects of coping strategies, locus of control, and self-efficacy on both social and academic integration. Moreover, quality of student interactions with other students, academic advisors, faculty, student services and administrative staff is influenced by normative beliefs as a function of self-directedness and autonomy. The findings supported evidence that programs that influence students’ coping strategies can encourage self-efficacy, which in turn reinforces academic interactions and indirectly influences academic integration, social integration, institutional fit and persistence. High Impact Practices (HIPs) such as first-year seminars and learning communities may enhance faculty and classroom academic interactions, and ultimately academic and social integration leading toward persistence. Faculty academic interactions and classroom academic interactions also facilitate social integration leading toward persistence. Overall, this study highlights a need for a better understanding of these interactions in order to help institutional administrators develop services and programs to better meet the needs of students, particularly in an era of teaching and learning in an online environment.