Teacher-directed and inquiry-based science instructional practices have been shown to influence students' performance on science assessments. However, only a small body of research has examined the associations of teacher-directed and inquiry-based science instructional practices with science-related dispositions among adolescent students using nationally representative samples drawn from countries across the globe. Hence, the present study, employing multilevel path analyses as an analytic strategy, investigated the relations of teacher-directed and inquiry-based science instruction to students' science-related dispositions, such as enjoyment of science, interest in broad science topics, instrumental motivation to learn science, science self-efficacy, and epistemological beliefs about science, among 428,197 adolescent students from 15,644 schools in 66 countries. Results of multilevel path analyses, after controlling for student-, school-, and country-level demographic and socio-economic factors, revealed that teacher-directed science instruction was significantly positively related to adolescent students' enjoyment of science, interest in broad science topics, instrumental motivation to learn science, science self-efficacy, and epistemological beliefs about science. Similarly, inquiry-based science instruction was also significantly positively linked to enjoyment of science, interest in broad science topics, instrumental motivation to learn science, and science self-efficacy. However, inquiry-based science instruction was not significantly associated with students' epistemological beliefs about science. The findings of the current study suggest that a blend of teacher-directed and inquiry-based science instruction may be more appropriate for developing and nurturing students' positive dispositions toward science. However, science teachers may require sufficient training and support to successfully implement the blended instruction model in their classrooms.