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Science education researchers and curriculum documents have advocated scientific inquiry for more than six decades; however, inconsistent findings concerning its effects on students' learning outcomes have been revealed in recent analyses of large-scale international assessment data (e.g., the Programme for International Student Assessment [PISA]). This has evoked considerable concern given the significant role that inquiry plays in science education. To unpack the complex influence of inquiry on science achievement, this study used the PISA 2015 data from eight Western or East Asian regions to explore the effects of inquiry on students' science achievement and the mediation of attitudes toward science. The results indicated that despite the negative effects that the investigation aspect of inquiry had on science achievement, the explanation aspect of inquiry had positive effects on science achievement for the Western, East Asian, and whole samples. When all of the effects of both the investigation and explanation aspects were integrated, the overall influence of inquiry on students' science achievement was found to be positive for the whole and East Asian samples and slightly negative for the Western sample. This study highlights the necessity of considering different facets of inquiry and different types of effects when investigating the effects of inquiry on science achievement and achieving a better balance between the investigation and explanation processes when implementing inquiry in school classrooms.