This study examined the opportunities and difficulties of online learning in Zambia’s higher education system, emphasizing the effects of self-regulation as a mediator between teacher-scaffolded online interactions and student learning engagement. Students and teachers frequently encounter significant challenges, such as low motivation, engagement, and self-regulation, despite the growing popularity of online learning. Hence, there was a need to explore how these can be mitigated through enhanced self-regulation and contribute to better educational outcomes and the broader context of pedagogical innovation. Data was gathered from an online survey of 1323 undergraduate students who took online courses in blended learning environments at four higher education institutions in Zambia. The results show a substantial mediating effect of self-regulation on student learning engagement and teacher-scaffolded online interactions. Findings underscore the need for comprehensive strategies to enhance online learning experiences, including constructive feedback, conducive learning environments, and continuous professional development programs for teachers. Furthermore, this study emphasizes the importance of interactive online learning activities to improve students’ learning management skills and promote self-discipline in online learning. It highlights the vital role of self-regulation, active learning engagement, and teacher-scaffolded online interactions and calls on educators and administrators to develop innovative ways to make participating in online learning smoother.