The study is in response to abrupt movement from the direct traditionally-centered classroom instruction to Elearning instruction in Ghana owing to the Corona Virus (COVID -19) pandemic. The study aimed at exploring the effect of E-learning interactivity on the effectiveness of E-learning in the Ghanaian context and ways of improving interactivity in E-learning models. The positivist research approach was adopted with cross-sectional survey as the research design. Using a web-based survey, a sample of 2,115 students were randomly selected from 194 different tertiary institutions in Ghana. Correlation and regression analysis was used as the statistical tools to answer the research questions set for the study. The results indicated that all the categories on E-learning interactivity (student-teacher interactivity, student-content interactivity, student–system interactivity, and studentstudent interactivity) correlated with course effectiveness, students’ independent learning skills and student learning behaviour respectively. However, the best predictor for course effectiveness was student–system interactivity, best predictor for students’ independent learning skills was student-student interactivity while the best predictor of students’ learning behaviour was student-teacher interactivity. The study reiterated that the relationship between different forms of E-learning interactivity have significant impact on course effectiveness, students’ independent learning skills and students’ learning behaviour. Practical implications and suggestions were made in order to enhance the levels of interactivity within E-learning models