Demonstrating higher-order thinking skills is crucial for thriving in a volatile, uncertain, complex, and ambiguous (VUCA) environment. In science education, inquiry-based learning has increasingly been recognized as a potent approach to stimulate students' higher-order thinking skills. While prior research has shown evidence of its positive impact on student achievement, no study has critically synthesized its effect on students' higher-order thinking skills in the context of science learning. Thus, this study conducted a meta-analysis following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) protocol. The study extracted twenty-six (26) effect sizes from twenty (20) studies, involving 1,349 students exposed to both inquiry-based and conventional approaches. Using the Comprehensive Meta-analysis Software, effect size (Hedges g) was calculated to determine the magnitude of the effectiveness of inquiry-based approaches. The overall weighted effect size of g = 0.893 demonstrates that inquiry-based approaches have a significantly large and positive impact on students' higher-order thinking skills. Moderator analysis suggests that regardless of students' educational level, scientific discipline, or level of inquiry, the use of the inquiry-based approach in teaching scientific concepts maximizes students' higher-order thinking skills. Although various inquiry-based approaches were effective when combined with other instructional strategies for teaching scientific concepts, only a few studies integrated technology into the implementation of inquiry-based approaches in science. Given the positive findings of this meta-analysis, science teachers are further encouraged to adapt inquiry-based approaches to enhance their teaching practices and support students in strengthening their higher-order thinking skills.