BACKGROUND Undergraduate education constitutes a fundamental component of higher education and serves as a crucial indicator of institutional quality. Consequently, the reform of medical curricula, especially in the field of anesthesiology, is imperative. Such reform must effectively cater to both specialty trainees and non-specialty students on rotation, thereby enhancing the clinical relevance and educational impact of the discipline. This study aimed to evaluate the teaching effectiveness of a flipped classroom (FC) combined with case-based learning (CBL) approach in the ventilator management clerkship for non-anesthesiology undergraduate students. METHODS A total of 164 non-anesthesiology undergraduates (Class of 2021, five-year clinical medicine program) from Xiangya School of Medicine, Central South University, were enrolled. Using a random number table based on pre-existing clerkship groups, students were assigned to either the FC combined with CBL (FC-CBL) group (n = 87) or the traditional lecture-based learning (LBL) group (n = 77). The FC-CBL group completed pre-class video modules covering respiratory mechanics principles and ventilation mode recognition. During class, students worked in small groups to analyze typical cases of patients undergoing general anesthesia across three phases (induction, maintenance, and emergence), engaging in hands-on ventilator parameter adjustment training. Teaching satisfaction was assessed using a Likert 5-point scale. Learning outcomes were evaluated multidimensionally, including theoretical assessment, practice skills testing, and teaching satisfaction survey. RESULTS Compared to the LBL group, the FC-CBL group demonstrated significantly higher total theoretical scores (90.0 [80.0, 100.0] vs. 100.0 [80.0, 100.0], P = 0.024), total operational skill scores (80.0 [60.0, 95.0] vs.90.0 [80.0, 95.0], P = 0.016), and total teaching satisfaction scores (27.0 [24.2, 30.0] vs.30.0 [26.0, 30.0], P = 0.049). In the modular theoretical assessment, the FC-CBL group scored significantly higher than the LBL group in the "Basic Knowledge" module (30.0 [20.0, 40.0] vs. 40.0 [30.0, 40.0], P = 0.02). CONCLUSIONS The FC-CBL model, as an innovative teaching approach, effectively enhances theoretical knowledge, operational skills, and teaching satisfaction among non-anesthesiology undergraduates learning ventilator management, meriting wider application in anesthesiology clinical clerkships.