Water bodies can be polluted through different means, including microorganisms. This study was carried out to analyze physicochemical parameters, heavy metals concentrations, and bacterial pathogens in Andoni River, Rivers State, using 72, 18, and 120 water samples, respectively. Physical and chemical characteristics were examined on a periodic and seasonal basis. Only seasonally was the concentration of heavy metals examined. The heterotrophic plate count method was applied seasonally and periodically. Escherichia coli (E. coli) and other coliforms were found using the most probable number technique and the Eijkman test. Antibiotic profiling was done on verified E. coli isolates. Only temperature did not fall within the suggested standard values of the physicochemical parameters. In April, the temperature was at its maximum in the evenings. Cadmium, arsenic, chromium, and nickel concentrations were within the suggested limits, however mercury and lead concentrations were over the limits. Mercury concentrations were higher in April than in other months, while lead concentrations were higher in November. The highest count of heterotrophic bacteria observed was on the evening of July. Coliforms and E. coli were found in high numbers in both periods and seasons. Of the 139 isolates of E. coli subjected to antibiotic profiling, 102, 28, and 3 showed multiple antibiotic resistance indexes of 0.0, 0.1, and 0.2, respectively. This investigation discovered microorganisms, including E. coli, which is a sign of faecal pollution. In reality, chemical contaminants in the water body may have also contributed to E. coli's resistance to antibiotics.