Increased HIV/AIDS testing is of paramount importance in controlling the HIV/AIDS pandemic and subsequently saving lives. Despite progress in HIV/AIDS testing programmes, most people are still reluctant to test and thus are still unaware of their status. Understanding the factors associated with uptake levels of HIV/AIDS self-testing requires knowledge of people’s perceptions and attitudes, thus informing evidence-based decision making. Using the South African National HIV Prevalence, HIV Incidence, Behaviour and Communication Survey of 2017 (SABSSM V), this study assessed the efficacy of Generalised Linear Poisson Regression (GLPR) and Geographically Weighted Poisson Regression (GWPR) in modelling the spatial dependence and non-stationary relationships of HIV/AIDS self-testing uptake and covariates. The models were calibrated at the district level across South Africa. Results showed a slightly better performance of GWPR (pseudo R² = 0.91 and AICc = 390) compared to GLPR (pseudo R² = 0.88 and AICc = 2552). Estimates of local intercepts derived from GWPR exhibited differences in HIV/AIDS self-testing uptake. Overall, the output of this study displays interesting findings on the levels of spatial heterogeneity of factors associated with HIV/AIDS self-testing uptake across South Africa, which calls for district-specific policies to increase awareness of the need for HIV/AIDS self-testing.