Academic performance of students is global issue of great concern to educators. This study sought to ascertain the effect of STEM problem-based learning as an inquiry approach on secondary school student's performance in Biology at government-owned secondary schools in Kebbi State, Nigeria. The non-equivalent control group design was adopted. Two schools were selected in which purposive sampling was employed to select the participants. Each class contain 40 participants. The data was obtained using Diffusion and Osmosis Achievement Test (DOAT). The variables were evaluated using descriptive statistics and the Independent Samples t-test. Based on the results obtained the STEM Problem-Based Learning (STEM-PBL) have a significant and favorable impact on students' biology achievement and that students in the experimental group retained more Biology information compared to the control group. The study recommended among others that, Biology classes should be made more engaging to students and teachers need to be more creative and inventive when it comes to discovering, selecting, and implementing activity-based instructional strategies in the classroom.