Patient satisfaction is a widely used indicator of assessing health care quality and has been used by policymakers to consider the needs of patients when developing suitable strategies for safe and high-quality care. However, in South Africa, the dual burden of HIV and NCDs has implications for the health system, whereby the factors influencing the quality of care and patient satisfaction may be unique to this context. Thus, this study examined the predictors affecting chronic disease patients' levels of satisfaction with care in Johannesburg, South Africa. A cross-sectional study was conducted among 2,429 chronic disease patients at 80 primary healthcare facilities in Johannesburg, South Africa. A questionnaire derived from existing literature and patient satisfaction frameworks was used to measure the level of satisfaction of patients when receiving care. Patients' overall satisfaction was categorized into not satisfied and satisfied. Cronbach's alpha was used to assess scale reliability. Factor analysis was used as a data dimension reduction approach and the Kaiser-Meyer-Olkin and the Bartlett test of sphericity were used to test the sampling adequacy and to examine the inter-independence of the items. Logistic regression was used to determine factors associated with being satisfied. Significance was set at 5%. The majority of chronic disease patients 65.5% (n = 1,592) were aged 18-30 years; 63.8% (n = 1,549) were females, 55.1% (n = 1,339) were married and 2,032 (83.7%) were satisfied with care. The factor analysis results were in five sub-scales namely improving values and attitudes, cleanliness of the clinic, safe and effective care, infection control, and on the availability of medicines. In adjusted models, patients aged >51years had an increased odds of 3.18 (95% CI:1.31-7.75) of being satisfied compared to those aged 18-30 years and patients who had visited the clinic at least 6 times had 51% increased odds of being satisfied (AOR = 1.51,95% CI:1.13-2.03). The odds of being satisfied increased by 28% (AOR = 1.28,95% CI:1.07-1.53), 45% (AOR = 1.45,95% CI:1.2-1.75), 34% (AOR = 1.34,95% CI:1.13-1.59) and 4.31 (95% CI:3.55-5.23) for every score increase in the factors like improving values and attitudes, cleanliness of clinic safe and effective care and availability of medicine, respectively. Key predictors of patient satisfaction were found to be sociodemographic factors including age, distance to the clinic, number of visits and waiting times as well as factors such as improving values and attitudes, cleanliness of the clinic, waiting time, safety and effective care and availability of medicines. Adjustment of existing frameworks for addressing context-specific improvement of patient experiences such as security and safety is recommended to ensure healthcare quality and service utilization for better chronic disease outcomes in South Africa.