Objective: HIV remains a global burden, with the Sub-Saharan Africa (SSA) region reporting the largest number of people living with HIV/AIDS (PLHIV). An exponential improvement in the accessibility and uptake of antiretroviral treatment across SSA has significantly improved outcomes for PLHIV. Hence, HIV care goals have shifted from reducing mortality and morbidity to improving health-related quality of life (HRQoL). This study uses generic and condition-specific HRQoL outcomes to holistically determine the HRQoL of Zimbabwean adult PLHIV and associated factors. HRQoL is a dynamic subject construct that warrants continuous evaluation to provide meaningful feedback to various stakeholders. We enrolled 536 adults PLHIV in Zimbabwe. Collected data were analyzed through descriptive statistics and multivariate binary logistic regression. Results: Our study shows a high HRQoL perception by Zimbabwean PLHIV. Anxiety, depression, and poor environmental health were widely reported domains influencing HRQoL. Also, being aware of HIV status for over a year, not experiencing an adverse event, being married, having adequate finances and food security and having higher educational status were associated with higher HRQoL. It is essential to integrate mental health care into routine HIV care to improve treatment outcomes and HRQoL. Last, implementing bespoke multisectoral HRQoL-enhancement interventions is paramount.