Coastal ecosystems are increasingly impacted by man-made disturbances including pollution from agriculture, aquaculture and municipal waste. This study employed multiple ecological indicators to assess environmental quality of the Densu Estuary and understanding of environmental controls on the spatial distribution of organisms. Physicochemical parameters were measured in situ. Water and sediment samples were collected from ten stations and analysed for nutrients, total suspended solids and organisms using standard methods. The water quality index for the Densu Estuary ranged from 359.5 to 484.4, suggesting an unhealthy ecosystem. The abundance of indicator species, e.g. faecal bacteria (Escherichia coli, Enterococcus species) and polychaetes (Capitella and Nereis species) varied significantly (p<0.05) among stations. Contaminated sites are located landwards with high human impacts. Faecal bacteria and polychaete abundance correlated significantly (p<0.05) with the respective physicochemical parameters. Canonical analysis (74.11%) showed the physicochemical influence on the spatial distribution of species. The pH significantly (p<0.05) controlled the spatial distribution of faecal bacteria and polychaetes in the Densu Estuary. The results suggest environmental pollution in the Densu Estuary, useful baseline information for effective legislation towards its sustainable management.