The study investigated the relationship between domestic violence and girl child self-esteem in secondary schools of Nyakishana Sub County, Buhweju District, Uganda. The objectives of the study were to determine the degree of girl child self-esteem, examine the level of domestic violence, and establish the relationship between domestic violence and self-esteem. The study employed a descriptive research design combining both quantitative and qualitative approaches. A total of 106 respondents, including students, class teachers, the headteacher, the Director of Studies, and selected household representatives, participated in the study. Data were collected using questionnaires, interviews, and observation, and analyzed using descriptive statistics and multiple linear regression. The results revealed that teacher support, peer relationships, parental encouragement, and a conducive school environment significantly influenced the degree of girl child self-esteem, with approximately 69.8% of the variance in self-esteem explained by these factors (R² = 0.698, p < 0.01). Analysis of domestic violence showed a high prevalence in the study area, with parental conflict, alcohol abuse, poverty, and cultural gender norms identified as significant contributors (R² = 0.729, p < 0.001). A strong negative relationship was established between domestic violence and girl child self-esteem (R² = 0.671, p < 0.01), indicating that exposure to emotional, physical, and economic abuse significantly lowered girls’ confidence, academic engagement, and psychological well-being. Emotional violence emerged as the most detrimental form, followed by physical violence and neglect. It was concluded that domestic violence significantly undermined the self-esteem of the girl child, while supportive teachers, peers, parents, and a positive school environment enhanced confidence and emotional resilience. The study recommended that schools and communities implement psychosocial support programs, strengthen counseling services, promote gender equality education, sensitize parents on non-violent parenting, ensure safe and inclusive learning environments, and provide socio-economic support to vulnerable families. By addressing both school-based and household factors, girls’ self-esteem, academic performance, and overall well-being could be significantly improved.