Online case-based learning (CBL) is a method used by King Abdulaziz University to teach medical students in their preclinical years. The use of CBL in basic sciences is important for enabling medical students to correlate basic sciences with future clinical practice. This study implemented online CBL for biochemistry teaching as part of the medical genetic module for 3rd-year preclinical students. Teaching during the study was completely online because of restricted precautions caused by the COVID-19 pandemic, except for practical sessions that were held on campus. The case was presented to the students involved in prenatal screening and diagnosis. Students were guided to learn and discuss the biochemical tests used for prenatal screening and diagnosis and their clinical importance. They were divided into two groups: the control group was given an online lecture and the intervention group was given an online CBL session before the lecture. The online lecture was given to both groups simultaneously by the same instructor, and then 10 MCQs tests were distributed to both groups after the lecture, and their test scores were compared. A 10-question survey was administered to the intervention group to assess their perception of the online CBL session after the test. A significant difference was found between the intervention and control groups regarding test scores (p < 0.001), and most students found the online CBL session enjoyable and motivating.