Due to the learning difficulties in mathematics education, a new teaching methodology have been proposed for its improvement. Difficulties in mathematics learning indicate that students are not able to properly deal with resolving calculations and/or problems. This research examines the evolution of the attitudes of pre-service teachers’ (PSTs) toward mathematics learning when an open calculation based on numbers (OCN) method was followed in a flipped classroom. It was conducted in a general mathematics course, Primary Education bachelor’s degree during the course of 2019/2020. A total of 143 students participated in the study (230 students enrolled), with a pre- and post-test survey questionnaire. Based on the analysis of survey questionnaires, the obtained results demonstrated that the attitudes (own beliefs and conceptions (OB), positive (ATP), and negative (ATN) attitudes) of PSTs improved positively after completing the flipped-OCN method toward mathematics learning. Regarding the statistical analyses, all questions had a significant difference that showed the influence of the flipped-OCN method, improving the PSTs attitudes toward mathematics learning (p < 0.005). According to the structural equation modeling—partial least squares (SEM-PLS) analysis, it demonstrated that the components relation effects of OB, ATP, and ATN of PSTs toward mathematics learning, and the influence of their educational background. Finally, with the principal component analysis (PCA), it can be found out that the science and technology background were positively correlated after the flipped-OCN method comparing with the rest of PSTs. The influence of the proposed method indicated a significant improvement in these components. Therefore, the results concluded that this study allowed to draw a promising tendency about the PSTs’ attitudes toward mathematics learning with the OCN method in the flipped classroom. Additionally, these outcomes could advance our comprehension of how to help pre-service education for teachers’ enhancement and maturity of positive attitudes about themselves as future teachers. Then, it would be a fundamental piece in building logical and critical thinking and development for children.