Active learning is a pedagogical approach that involves students engaging in collaborative learning, which enables them to take more responsibility for their learning and improve their critical thinking skills. While prior research examined student performance at majority universities, this study focuses on specifically Historically Black Colleges and Universities (HBCUs) for the first time. Here we present work that focuses on the impact of active learning interventions at Florida A&M University, where we measured the impact of active learning strategies coupled with a SCALE-UP (Student Centered Active Learning Environment with Upside-down Pedagogies) learning environment on student success in General Biology. In biology sections where active learning techniques were employed, students watched online videos and completed specific activities before class covering information previously presented in a traditional lecture format. In-class activities were then carefully planned to reinforce critical concepts and enhance critical thinking skills through active learning techniques such as the one-minute paper, think-pair-share, and the utilization of clickers. Students in the active learning and control groups covered the same topics, took the same summative examinations and completed identical homework sets. In addition, the same instructor taught all of the sections included in this study. Testing demonstrated that these interventions increased learning gains by as much as 16%, and students reported an increase in their positive perceptions of active learning and biology. Overall, our results suggest that active learning approaches coupled with the SCALE-UP environment may provide an added opportunity for student success when compared with the standard modes of instruction in General Biology.