Knowledge and practices of rural South African populations with regard to antibiotic access and use (ABACUS) remain understudied. By using the case of four villages in the north east of the country, our aim was to investigate popular notions and social practices related to antibiotics to inform patient-level social interventions for appropriate antibiotic use. To achieve this, we investigated where community members (village residents) were accessing and sourcing medication, and what they understood antibiotics and antibiotic resistance (ABR) to be. Embedded within the multicountry ABACUS project, this qualitative study uses interviews and focus group discussions. A sample of 60 community members was recruited from the Agincourt Health and Demographic Surveillance System, situated in Mpumalanga Province, from April to August, 2017. We used the five abilities of seek, reach, pay, perceive, and engage in access to healthcare as proposed by Levesque's "Access to Healthcare" framework. Respondents reported accessing antibiotics prescribed from legal sources: by nurses at the government primary healthcare clinics or by private doctors dispensed by private pharmacists. No account of the illegal purchasing of antibiotics was described. There was a mix of people who finished their prescription according to the instructions and those who did not. Some people kept antibiotics for future episodes of infection. The concept of "ABR" was understood by some community members when translated into related Xitsonga words because of knowledge tuberculosis and HIV/AIDS treatment regimens. Our findings indicate that regulation around the sale of antibiotics is enforced. Safer use of antibiotics and why resistance is necessary to understand need to be instilled. Therefore, context-specific educational campaigns, drawing on people's understandings of antibiotics and informed by the experiences of other diseases, may be an important and deployable means of promoting the safe use of antibiotics.