The preliminary consequence of pollutants in water is to reduce the quality of water although this may not be immediately noticeable because of the self-purifying ability of some water bodies. The study on the physicochemical characteristics, bacteriological, and macrobenthic invertebrates was carried out in the Orogodo River. All the examined physicochemical characteristics of the water showed no significant difference (p > 0.05) across the stations. For the heavy metals, it was in decreasing order as follows: station 2 > station 3 > station 1. All the heavy metals except nickel had high values upstream (station 1). Bacteriological examination of the water revealed the presence of mesophilic bacteria across the stations at p < 0.01 (a highly significant difference). E. coli varied significantly (p < 0.01) across the stations. However, a further evaluation using the DMR test revealed that the population recorded at station 3 was significantly higher than that recorded at stations 1 and 2. A total of 787 macrobenthic invertebrates comprising 44 macroinvertebrates’ taxa were recorded. Most of the macrobenthic faunas observed were distributed across the three stations except the chironomids, the rat-tailed maggot (Eristalis tenax), and the family Hirudinea whose occurrence was almost restricted to station 2. This revealed an ecological impact because this species is a basic indicator of an ecosystem sentinel. Sorenson’s quotient of faunal similarity showed that macrobenthic fauna at these three stations was similar. The similarity was the highest between stations 1 and 3 (75.0%) and the lowest between stations 1 and 2 (50.0%). The biological monitoring working party (BMWP) score system showed that station 2 was moderately polluted, while stations 1 and 3 were only slightly affected. At stations 1, 2, and 3, the arithmetic WQI (water quality) values were 900.99, 1010.10, and 951.20, respectively. The high values of WQI obtained across the stations were attributable to the concentrations of Fe, Cu, Cr, Cd, Ni, Pb, V, and THC, thus reiterating the conclusion drawn from the physicochemical parameter analysis. Boiling the water before consumption is highly recommended to avoid possible human health problems, especially effects from microbial pathogens like coliforms and E. coli.