<b>Background:</b> In Africa, true prevalence of chronic kidney disease (CKD) is unknown, and associated clinical and genetic risk factors remain understudied. This population-based cohort study aimed to investigate CKD prevalence and associated risk factors in rural South Africa. <b>Methods:</b> A total 2021 adults aged 20-79 years were recruited between 2017-2018 from the Agincourt Health and Socio-Demographic Surveillance System in Bushbuckridge, Mpumalanga, South Africa. The following were collected: sociodemographic, anthropometric, and clinical data; venous blood samples for creatinine, hepatitis B serology; DNA extraction; spot urine samples for dipstick testing and urine albumin: creatinine ratio (UACR) measurement. Point-of-care screening determined prevalent HIV infection, diabetes, and hypercholesterolemia. DNA was used to test for apolipoprotein L1 ( <i>APOL1</i>) kidney risk variants. Kidney Disease Improving Global Outcomes (KDIGO) criteria were used to diagnose CKD as low eGFR (<60mL/min/1.73m ²) and /or albuminuria (UACR ≥ 3.0mg/mmol) confirmed with follow up screening after at least three months. eGFR was calculated using the CKD-EPI _(creatinine) equation 2009 with no ethnicity adjustment. Multivariable logistic regression was used to model CKD risk. <b>Results:</b> The WHO age-adjusted population prevalence of CKD was 6.7% (95% CI 5.4 - 7.9), mostly from persistent albuminuria. In the fully adjusted model, <i>APOL1</i> high-risk genotypes (OR 2.1; 95% CI 1.3 - 3.4); HIV infection (OR 1.8; 1.1 - 2.8); hypertension (OR 2.8; 95% CI 1.8 - 4.3), and diabetes (OR 4.1; 95% CI 2.0 - 8.4) were risk factors. There was no association with age, sex, level of education, obesity, hypercholesterolemia, or hepatitis B infection. Sensitivity analyses showed that CKD risk factor associations were driven by persistent albuminuria, and not low eGFR. One third of those with CKD did not have any of these risk factors. <b>Conclusions:</b> <i> </i>In rural South Africa, CKD is prevalent, dominated by persistent albuminuria, and associated with <i>APOL1</i> high-risk genotypes, hypertension, diabetes, and HIV infection.