With the increasing spread of antimicrobial resistance, there is growing attention to the contribution made by drinking water systems. The potential health impact of two drinking water treatment and distribution systems (A and B) in the North-West Province of South Africa was determined by investigating the water quality and occurrence of antimicrobial-resistant heterotrophic bacteria and genes in the raw and treated water over four seasons. Most of the physicochemical parameters except for electrical conductivity were within permissible limits. Coliform bacteria reduced from raw to potable water except for counts higher than the threshold recorded in Summer and Winter. A total of 203 heterotrophic bacterial isolates were recovered on chromogenic R2A medium and subjected to susceptibility testing to twelve antibiotics. Most of the isolates were resistant to β-lactam antibiotics and Trimethoprim, whereas they were susceptible to Ciprofloxacin, Erythromycin, and Neomycin. The proportions of Cephalothin and Kanamycin-resistant isolates were significantly higher (p < 0.05) after treatment for site A, compared to significantly lower β-lactam, Oxytetracycline, and Trimethoprim-resistant isolates for B. Over 50% of isolates were of high risk, indicating their origin from high antibiotic-use sources. Seventy-one (35%) isolates were multidrug-resistant, out of which the majority (53.5%, n = 38) possessed the strA gene, followed by strB 21 (29.6%), dfrB 13 (18.3%), aadA 11 (15.5%), blaCTX-M 5 (7.0%), and tetA 3 (4.2%). The 16S rRNA gene sequences of the isolates revealed strains belonging to eight bacterial families, some of which are clinically important.