The current study aimed at investigating the impact of Flipped Classroom Strategy by using E-Learning Systems (Blackboard) based on Critical Thinking Skills of the acquisition of fresh female students of the derivative concept of Calculus. To conduct this study, the researchers followed the explanatory sequential mixed-methods by dividing randomly the 54 fresh female students from the University of Bisha into two equal groups: the experimental group and the control group. The selection was based on their achievement in First Exam. To measure students' acquisition of the derivative concept, the researchers relied on a post-test, and semi-structured interview with some learners. The analysis of the obtained data showed that teaching Calculus using Flipped Classroom Strategy that based on Critical Thinking Skills is better than the traditional teaching methodology in the acquisition derivative concept. In fact, the interviews show that the fresh female students in the experimental group preferred the new strategy, and said that it makes learning mathematics interesting and easier.