According to the Centre for Disease Dynamics Economics and Policy, South Africa represents a paradox of antibiotic management similar to other developing countries, with both overuse and underuse (resulting from lack of access) of antibiotics. In addition, wastewater reuse may contribute towards antibiotic resistance through selective pressure that increases resistance in native bacteria and on clinically relevant bacteria, increasing resistance profiles of the common pathogens. Sediments of surface water bodies and wastewater sludge provide a place where antibiotic resistance genes are transferred to other bacteria. Crop irrigation is thought to be a potential source of exposure to antibiotic-resistant bacteria through the transfer from the water or sludge into crops. The objectives of this study were to examine the antibiotic-resistance profiles of Escherishia coli from three agricultural locations in the Western Cape, South Africa. Using a classical microbiology culture approach, the resistance profiles of E. coli species isolated from river water and sediments, farm dams and their sediments and a passive algal wastewater treatment ponds and sediment used for crop irrigation were assessed for resistance to 13 commonly used antibiotics. Randomly selected E. coli isolates from the sediment and water were tested for resistance. 100% of E. coli isolates were resistant to sulphamethoxazole, highlighting its relevance in the South African context. In river water and farm dam samples, only the E. coli isolated from sediment were found to be resistant to fluoroquinolone or fluorifenicol. In the wastewater treatment ponds, the resistance profiles of E. coli isolated from sediments differed from those isolated from effluent, with 90% of the effluent isolates being resistant to ampicillin. Isolates from the sediment were less resistant (40%) to ampicillin, whereas all the isolates from the pond water and sediment samples were resistant to sulphamethoxazole. These results illustrate the importance of developing a better understanding of antibiotic resistance in agriculture and wastewater scenarios to ensure remedial measures take place where the greatest benefit can be realised especially in countries with limited financial and infrastructural resources. Moreover, the potential for passive algal treatment as an effective, feasible alternative for wastewater treatment is highlighted, with comparable resistance profiles and a reducing overall resistance in the sediment samples.