BACKGROUND: Active family support helps as a buffer against adverse life events associated with antiretroviral therapy (ART) uptake and adherence. There is limited data available to explain how family support shapes and affects individual healthcare choices, decisions, experiences, and health outcomes among youth living with HIV (YLWH). We aimed to describe family support patterns and its role in viral load suppression among YLWH at a rural hospital in southwestern Uganda. METHODS: We performed a mixed-method cross-sectional study between March and September 2020, enrolling 88 eligible YLWH that received ART for at least 6 months. Our primary outcome of interest was viral load suppression, defined as a viral load detected of ≤500 copies/mL. Data analysis was performed using Statistical Package for Social Sciences version 20. Fifteen individuals were also purposively selected from the original sample and participated in an in-depth interview that was digitally recorded. Generated transcripts were coded and categories generated manually using the inductive content analytic approach. All participants provided written consent or guardian/parent assent (those <18 years) to participate in the study. RESULTS: Forty-nine percent of YLWH were females, the median age was 21 (IQR: 16-22) years. About half of the participants (53%) stayed with a family member. A third (34%) of participants had not disclosed their status to any person they stayed with at home. Only 23% reported getting moderate to high family social support (Median score 2.3; IQR: 1.6-3.2). Seventy-eight percent of YLWH recorded viral load suppression. Viral load suppression was associated with one living with a parent, sibling, or spouse (AOR: 6.45; 95% CI: 1.16-16.13; P = .033), having a primary caretaker with a regular income (AOR: 1.57; 95% CI: 1.09-4.17; P = .014), and living or communicating with family at least twice a week (AOR: 4.2; 95% CI: 1.65-7.14; P = .003). Other significant factors included youth receiving moderate to high family support (AOR: 12.11; 95% CI: 2.06-17.09; P = .006) and those that perceived family support in the last 2 years as helpful (AOR: 1.98; 95% CI: 1.34-3.44; P = .001). HIV stigma (AOR: 0.10; 95% CI: 0.02-0.23; P = .007) and depression (AOR: 0.31; 95% CI: 0.06-0.52; P = .041) decreased viral load suppression. Qualitative data showed that dysfunctional family relationships, economic insecurity, physical separation, HIV- and disclosure-related stigma, past and ongoing family experiences with HIV/ART affected active family support. These factors fueled feelings of abandonment, helplessness, discrimination, and economic or emotional strife among YLWH. CONCLUSION: Our data showed that living with a family member, having a primary caretaker with a regular income, living or communicating with family members regularly, and reporting good family support were associated with viral load suppression among YLWH in rural southwestern Uganda. Experiencing depression due to HIV and or disclosure-related stigma was associated with increased viral load. All YLWH desire ongoing emotional, physical, and financial support from immediate family to thrive and take medications daily and timely. Future interventions should explore contextual community approaches that encourage acceptance, disclosure, and resource mobilization for YLWH who rely on family support to use ART appropriately.