Despite advances made in HIV prevention and treatment interventions in South Africa, barriers to their utilization continue to exist. Understanding perspectives from patients and providers of healthcare can shed light on the necessary strategies to enhance uptake of HIV services. A cross-sectional qualitative study was conducted in July 2020 in Ekurhuleni District. Based on HIV prevalence estimates from a national survey, male condom use coverage and antiretroviral treatment (ART) initiation rates from routinely collected clinical data for 2012, we selected facilities from geographical areas with varying HIV prevalence and uptake of HIV services. In-depth interviews were conducted with adult (≥18 years) patients and healthcare workers in selected primary healthcare facilities. Thematic analysis was performed following a framework built around the social cognitive theory to describe behavioural, personal, and social/environmental factors influencing utilization of HIV services. Behavioural factors facilitating uptake of HIV services included awareness of the protective value of condoms, and the benefits of ART in suppressing viral load and preventing mother-to-child HIV transmission which was evident across geographical areas. Barriers in high prevalence areas included suboptimal condom use, fears of a positive HIV result, and anticipated HIV-related stigma while seeking healthcare services. Across the geographical areas, personal factors included ability to correctly use available services enhanced by knowledge acquired during counselling sessions and community-based health promotion activities. Further, social support from family reinforced engagement in care. Compared to low uptake areas, clinics in high uptake areas used care-facilitators, outreach teams and decanting programs to address the environmental barriers including staff shortages and long queues. Barriers at multiple levels prevent optimal utilization of HIV services, calling for strategies that target and address the different levels and tailored to needs of specific settings. Overall, improved delivery of HIV prevention or treatment interventions can be achieved through strengthening training of healthcare providers in facilities and communities and addressing negative sequelae from utilising services in low uptake areas.