Objective: To explore the application of progressive case teaching combined with scenario simulation in the comprehensive practical teaching of nursing in higher vocational colleges. Methods: From September 2023 to November 2023, two groups of students were selected as the research objects. 36 students in the control group adopted the conventional nursing comprehensive practical training teaching method. Based on the conventional teaching method, 37 students in the observation group implemented the progressive case teaching combined with the scenario simulation method. The theoretical and operational test scores of the two groups of students were assessed and compared, and the teaching satisfaction and the score of critical thinking skills of the two groups of students were compared. Results: After the implementation of progressive case teaching combined with the scenario simulation method, the theoretical and operational test scores of students in the observation group were significantly better than those in the control group, with statistical significance (P < 0.05). The teaching satisfaction of the observation group was significantly higher than that of the control group (P < 0.05). The score of critical thinking skills of students in the observation group was significantly higher than that in the control group (P < 0.05). Conclusion: The application of progressive case teaching combined with scenario simulation in the teaching of nursing comprehensive practical training of higher vocational can effectively improve students’ theoretical and operational exam scores, promote the cultivation of their critical thinking skills, improve teaching satisfaction, and effectively enhance the quality of talent training for high-quality nursing majors.