This study aimed to assess perceptions among undergraduate medical students toward distance learning and its effects on their academic performance during the COVID-19 pandemic at Al-Qunfudhah College of Medicine, Umm Al-Qura University, KSA. A cross-sectional study was conducted among medical students at Al-Qunfudhah College of Medicine, Umm Al-Qura University, KSA, during the 2020-2021 academic year. Data were collected through a predesigned, well-structured online survey from (1st March to 31th May 2021). A sample of 223 undergraduates responded to an online survey, with a response rate of 74.3%; female students represented 54.3%. Blended education was preferred by most students (73.1%). Moreover, 72.2% of students perceived that distance learning saved their time, and approximately two-thirds (61.4%) were stimulated by the availability of lecture recordings. Approximately 59% and 54% reported that distance learning was more comfortable and improved their technology skills, respectively. Poor communication (66%) and network problems (61.4%) were the most common challenges in distance learning. Nonetheless, a substantial increase (P = 0.001) in students' grade point averages was observed with distance learning. Most medical students preferred blended education combining the advantages of both traditional and distance learning strategies. The availability of educational materials, improvements in students' technological skills and time saving were the most perceived benefits of distance learning among students. However, the main obstacles were internet problems, poor communication and deprivation from real clinical practice. Despite the improvement in students' grade point averages during distance learning compared with traditional learning, blended education was recommended by the majority or participants.