In this study, two sections of undergraduate Introductory Anatomy and Physiology taught in the traditional face-to-face format (n = 58) was compared to two hybrid classes (n = 38) using the flipped-classroom model taught by the same instructor. Formative and summative examination scores were compared to determine the effect of the different learning methods. Our results revealed no significant difference between the mean scores of summative examinations and between the traditional and hybrid classes (p > 0.05). Of five quizzes administered, students taught in the traditional format scored significantly higher in only one of five quizzes. In addition, comparison of in-class laboratory examination scores showed no difference (P > 0.05) in three out of four. However, student evaluations of the hybrid classes were more positive as determined by end-of-course evaluations (4.54 versus 2.9 on a 1–5 Likert scale). This is the first study that compares a hybrid versus a traditional science course at a historically black college or university. We conclude that comparison of student outcomes in traditional versus hybrid Anatomy and Physiology I classes were similar. At a time when all institutions of higher learning have adopted online learning and distance learning due to the COVID-19 pandemic, this is a timely comparison.