© The Author(s) 2019. This study investigated the antibacterial resistance profiles of E. coli pathotypes isolated from children under five years and drinking water samples collected from the North West Province of South Africa and ascertained the clonality of the isolates. Two hundred and forty-one E. coli isolates were recovered from stool samples of diarrhoeic and non-diarrhoeic children under five years old, and drinking water, using the Colilert-18 ® Quanti-tray/2000 and Eosin methylene blue agar. The presence of enteropathogenic (eaeA), enterohaemorrhagic (eaeA,stx1, stx2 and flicH7), enteroaggregative (eagg), enteroinvasive (ipaH) and enterotoxigenic (ST and LT) E. coli pathotypes were also investigated using PCR. Antibiotic susceptibility was carried out through the disk diffusion method. The presence of blaCTX-M, blaSHV, blaCMY, and blaDHA genes that code for β-lactamases was investigated using real-time PCR. Similarities between human and water isolates were tested using ERIC-PCR. Overall, EHEC (35.8%), EPEC/EHEC (22%), ETEC (21.6%) and EIEC (20.2%) were detected. The highest antibiotic resistance was detected to Clarithromycin (100%) and Erythromycin (100%) while the lowest resistance was against Gentamicin (0.4%). Also, 100% sensitivity was recorded to imipenem and meropenem. Multi-antibiotic resistance was observed in all the pathotypes, and the ESBL genes were detected in 71.6% of the pathotypes. ERIC-PCR indicated 100% similarities in some water and human samples. Pathogenic E. coli is amongst the diarrhoea-causing agents in the North West Province with EHEC being the most identified pathotype. The clonal relatedness of the human and water isolates suggests that domestic water might be a route of transmission.