We assessed the prevalence, distribution, and antibiotic resistance patterns of Escherichia coli and Enterococcus spp. isolated from raw and treated wastewater of a major wastewater treatment plant (WWTP) in KwaZulu-Natal, South Africa and the receiving river water upstream and downstream from the WWTP discharge point. Escherichia coli and enterococci were isolated and counted using the Colilert®-18 Quanti-Tray® 2000 and Enterolert®-18 Quanti-Tray 2000 systems, respectively. A total of 580 quantitative PCR-confirmed E. coli and 579 enterococci were randomly chosen from positive samples and tested for in vitro antibiotic susceptibility using the disk diffusion assay against 20 and 16 antibiotics, respectively. The removal success of the bacterial species through the treatment procedure at the WWTP was expressed as log removal values (LRVs). Most E. coli were susceptible to meropenem (94.8%) and piperacillin-tazobactam (92.9%), with most Enterococcus susceptible to ampicillin (97.8%) and vancomycin (96.7%). In total, 376 (64.8%) E. coli and 468 (80.8%) Enterococcus isolates showed multidrug resistance (MDR). A total of 42.4% (246/580) E. coli and 65.1% (377/579) enterococci isolates had multiple antibiotic resistance indices >0.2. The LRV for E. coli ranged from 2.97 to 3.99, and for enterococci the range was observed from 1.83 to 3.98. A high proportion of MDR E. coli and enterococci were present at all sampled sites, indicating insufficient removal during wastewater treatment. There is a need to appraise the public health risks associated with bacterial contamination of environmental waters arising from such WWTPs to protect the health of users of the receiving water bodies.