This study examined the relationship between teachers’ professional responsibility, teacher–learner relationships, and school performance in primary schools of Nyakinama Sub-County, Kisoro District, Uganda. Anchored in McGregor’s Theory X and Theory Y, the study adopted a descriptive cross-sectional research design using mixed methods. Data were collected from 140 respondents comprising teachers, head teachers, and district education officials through questionnaires and interview guides. Quantitative data were analyzed using descriptive statistics and Pearson’s correlation analysis, while qualitative data were analyzed thematically. Findings revealed positive but weak and statistically significant relationships between teachers’ professional responsibility and school performance (r = 0.197, p < 0.05), as well as between teacher–learner relationships and school performance (r = 0.277, p < 0.05). The results indicate that while professional responsibility and positive interpersonal relationships contribute to improved academic performance, discipline, and participation in co-curricular activities, their overall influence is modest. The study concludes that enhancing school performance requires integrated approaches that combine professional responsibility with broader institutional and contextual interventions.