The resistance of different pathogenic variants of E. coli to antibiotics, is a health concern globally. The study assessed the resistance of 90 E. coli isolates that survived chlorination at a Wastewater Treatment Plant (WWTP) in North West, South Africa (NW-SA), to 12 different antibiotics using the Kirby-Bauer disk diffusion method. The study further assessed the diarrheagenic pathotypes origin of the isolates. The molecular characterization revealed diarrheagenic E. coli pathotypes ranged as follows: Enteroaggregative E. coli (EAEC) 16 (17.78%), Enteroinvasive E. coli (EIEC) 6 (6.67%), Enterotoxigenic E. coli (ETEC) 5 (5.56%) and Enteropathogenic E. coli (EPEC) 3 (3.33%). A high degree of resistance was observed against sulphamethoxazol (92.22%), while lower resistance was observed against Kanamycin (3.33%), chloramphenicol (5.56%) and ciprofloxacin (6.67%). Multiple drug resistance of three and more antibiotics was observed in 81.11% of the E. coli isolates. The detected diarrheagenic E. coli pathotypes showed multiple resistance to different studied antibiotics with Multiple Antibiotic Resistance Indexing (MARI) equal to 0.9 for EIEC and EAEC respectively, followed by ETEC at 0.8 and EPEC at 0.2. The study reveals that the wastewater effluent from the studied plant serves as an important reservoir for the distribution of antibiotic resistant diarrheagenic E. coli pathotypes and other potential pathogens to the aquatic milieu, thus confirming potential risk to public health.