This research aimed to determine the effectiveness of Creative Entrepreneurship Learning Based on Discovery Skills (CEL-BaDiS) in improving students' creative-thinking skills on the simple food biotechnology topic. This research is a quasiexperiment using the pretest-posttest control-group design in a state university in Surakarta, Indonesia in the 2018/2019 academic year with one class as an experimental class using the CEL-BaDiS model and the other class as the existing class using a Project-Based Learning (PjBL) model. The data were obtained using an essay test instrument to measure creative-thinking skills through expert validations, namely validation from the education and evaluation expert, biotechnology expert, and certified science lecturer, as well as an empirical validation through trials. The results demonstrated that the average score of the score gain calculation of creative-thinking skills in the experimental class was higher by 0.65 compared to that of the existing class of 0.52. The independent sample t-test shows the difference between the experimental class and the existing class with the t value of 2.1491. Based on the findings, it can be summed up that creative-thinking skills in flexibility, fluency, originality, and elaboration aspects can be improved effectively through the activities of the CEL-BaDiS model.