Child-headed households (CHHs), in which adolescents assume adult responsibilities after losing or being abandoned by their parents, pose a growing challenge to educational equity in Zimbabwe’s Manicaland Province. In this context, HIV/AIDS, economic migration, and the breakdown of extended kinship networks have led to an estimated 15,000–20,000 such households. This study investigates which school-based support strategies most effectively improve educational outcomes and well-being among secondary school students from CHHs. Using a convergent parallel mixed-methods approach grounded in Bronfenbrenner’s Ecological Systems Theory, quantitative data were collected via structured surveys completed by 18 teachers and administrators regarding 40 CHH students across six secondary schools in the Mutare and Mutasa districts. Qualitative data were obtained through semi-structured interviews with 12 teachers and 10 students. The results show that comprehensive support combining material aid, academic tutoring, psychosocial counseling, and flexible attendance and assessment policies significantly improves attendance (Cohen’s d = 1.12), academic performance (d = 0.89), and well-being (d = 1.04) compared with fragmented, single-component efforts. These effect sizes far exceed typical benchmarks for educational interventions, yet only 30% of students received this support, indicating that current practices are fragmented. The qualitative analysis emphasizes the importance of respectful teacher-student relationships, the tension between household survival needs and a rigorous O- and A-level curriculum, and the critical role of collaboration among schools, NGOs, and communities. This points to the need for coordinated, multi-level support systems, formal government recognition of CHHs, flexible examination and attendance policies, and trauma-informed teacher training.