BACKGROUND: Critical thinking has been regarded as an essential skill for college students, which is especially imperative for medical students to possess the ability to have in-depth insight into complex clinical situations. Medical Immunology is an overarching principle connecting multiple medical subjects, which emphasizes that immunity is both beneficial and harmful to the host, thus putting higher demands on students' critical thinking. The utilization of Nobel Prize stories has been cited as a thematic framework for classroom teaching of other courses, showing numerous educational benefits. Therefore, this study rejuvenated a case-based teaching approach by creating and introducing a vibrant material library centered on numerous iconic Nobel Prize cases in Medical Immunology and evaluating its effects on the critical thinking of medical students. METHODS: A total of 70 second-year medical undergraduates from the Beijing University of Chinese Medicine were divided into a control group and an experimental group of 35 cases each. Throughout the semester, the control received the traditional teaching method, and the experimental group adopted case-based teaching based on the Nobel prize-centered material library. The process of teaching design and practice was described using "Antitoxin and immunoserum therapy" as a classical example. A unified assessment of the critical thinking dispositions of participants was conducted at the beginning and end of the semester using the Critical Thinking Disposition Inventory-Chinese Version (CTDI-CV). RESULTS: Intra-group longitudinal comparisons and inter-group parallel evaluations indicated that, compared with the conventional teaching approach, Nobel Prize case-based learning induced a statistically significant increase in the overall score of the CTDI-CV, as well as the scores within the subdimensions of truth-seeking, analyticity, and maturity in judgment (p < 0.05). Pearson correlation analysis further indicated a positive correlation between the total score of the CTDI-CV and the final grade (p < 0.05), which emphasized the crucial role of critical thinking dispositions in academic achievement. CONCLUSION: The case-based classroom teaching centered on Nobel Prize cases for Medical Immunology can effectively improve the critical thinking dispositions of medical undergraduates, which contributes to cultivating high-level medical and healthcare talents with excellent comprehensive quality in the new era.