This study examined the relationship between instructional supervision and students' academic performance at the Uganda Certificate of Education (UCE) level in selected public secondary schools of Kashari South, Mbarara City, Uganda. The study was guided by four specific objectives: to assess the relationship between professional development and students' academic performance; to examine the influence of feedback on students' academic performance; to determine the relationship between classroom observation and students' academic performance; and to assess the moderating role of teachers' experience on the relationship between instructional supervision and students' academic performance. The study was underpinned by the Instructional Leadership Theory, developed by Hallinger and Murphy. The theory's applicability lay in its emphasis on the pivotal role of school leaders in shaping teaching and learning through guiding, monitoring, and supporting teachers to improve student learning outcomes. It provided a lens to critically examine how supervisory practices such as classroom observations, mentoring, and feedback influenced educational outcomes within the local context of Kashari South. A cross-sectional research design was adopted, utilizing a mixed-methods approach. A sample of 152 respondents, including students, teachers, school administrators, and supervisors, was selected using simple random and purposive sampling techniques. Data were collected through questionnaires and interviews and analyzed using descriptive statistics, Pearson correlation, regression analysis, and thematic analysis. The results revealed several key findings. First, a strong positive and significant relationship was found between teachers' professional development and students' academic performance (r=0.696, p