ABSTRACT In the modern water management plans of nations that confront a severe lack of water resources, such as the Middle Eastern countries, the reuse of treated sewage water for agriculture is seen as an important alternative water supply. The goal of the current study was to use a lytic phage mixture to reduce both of Escherichia coli strains, coliforms, and other Enterobacteriaceae species in River Nile and drains outlets. The transmission electron microscope revealed morphological similarities between three novel phages (MCn4, MCn5, and MCn6) and those in the Siphoviridae, Myoviridae, and Podoviridae families. Escherichia coli ATCC® strain 11775 and Escherichia coli ATCC® strain 10536, the index coliform, were both lysed by these new phages. Different DNA polymerase (DP), tail protein (TP), and DNA polymerase accessory (DPA) gene sizes (2565 bp, 672 bp, and 951 bp, respectively) were reported by bioinformatics analyses, and all nucleotide sequences were recorded in the international GenBank. Phage-mediated bio-control in aquatic pathogenic bacteria relies on targeting various species and strains, with polyvalent MCn4, MCn5, and MCn6 phages exhibiting lytic effects on Salmonella typhi, Proteus vulgaris, and Citrobacter freundii strains. These phages had a significant lytic influence on the population of coliform bacteria after two hours of incubation. The study concluded that the use of this lytic coliphage mixtures for the decrease in coliform populations in sewage may be considered an efficient and cost-effective alternative to the expensive replacement of wastewater treatment plant equipment and infrastructure, as well as for controlling various bacterial pathogens could be achieved throughout few hours.