This study aimed to assess the public health risk of coliforms and E. coli contamination of potable water sources in Egypt. A total of 150 water samples (100 tap and 50 well) were collected from five districts in Gharbia governorate, Egypt. High rates of coliforms contamination were recorded in 52 and 76% of examined tap and well water samples, respectively. E. coli strains were detected in 16% of the water samples (15% tap water and 18% well water; 23.7% rural and 8.1% urban). Rural water sources were 3.5 times more likely to be contaminated than urban sources (P = 0.01). Eight (33.3%) E. coli isolates were Shiga toxin-producing E. coli (STEC). Multiple drug resistance (MDR) was observed for 62.5% of the isolates. Seven (29.2%) E. coli isolates harboured at least one of the extended-spectrum beta-lactamase (ESBL) genes. The majority (87.5%) of the STEC isolates were MDRs and harboured ESBL genes. STEC isolates were significantly more likely to resist six classes of antibiotics than non-STEC isolates. This is the first report of potable water contamination with MDR-STEC in Egypt. This study highlights an alarming public health threat that necessitates preventive interventions for public and environmental safety.