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This study examines the implementation of inquiry-based science instruction by lower primary teachers in Ghana under the Standards-Based Science Curriculum (SBSC). Utilizing an explanatory sequential mixed-methods design, it analyzes survey responses from 117 teachers alongside classroom observations and interviews with six urban and rural educators. Findings show uneven application of the 5E instructional model, with engagement and explanation more common than hands-on exploration or elaboration. Urban teachers exhibited greater use of inquiry strategies due to access to resources and training. Pedagogical Content Knowledge and contextual constraints shaped teaching practices. The results underscore the need for equitable support, tailored professional development, and realistic curriculum reform to enhance inquiry-based learning in underserved settings.