This study aims to develop a comprehensive system of pollution monitoring and control in the Nyabugogo catchment of Rwanda, which also includes the capital city, Kigali, through locating and highlighting pollution and its sources. Pollution hotspots were identified, covering areas of both anthropogenic and natural pollution. The study focused on water quality assessment especially the identification of the critical points of pollution (hotspots), by measuring selected physico-chemical parameters in the Nyabugogo River system. An extensive monthly water quality monitoring study was conducted from October 2008 to May 2009 and covered nutrients, organic and heavy metal pollutants. The parameters covered are Ammonium-Nitrogen (NH4 +-N), Nitric-Nitrogen (NO2—N), Nitrate-Nitrogen (NO3—N), Sulphates (SO4), Phosphates (PO4-P), Chemical Oxygen Demand (COD), Biological Oxygen Demand (BOD5), Dissolved Oxygen (DO), Total Dissolved Solids (TDS), Chromium (Cr), Iron (Fe), Lead (Pb), Manganese (Mn), Zinc (Zn), Conductivity (EC), pH, and Turbidity. The samples were collected, preserved and analyzed in the laboratory using standard methods whilst TDS, conductivity, turbidity and pH were measured in the field using HACH field kits. The water quality study revealed that both urbanized and rural sub-catchments have serious but different types of pollution. For example, the water from rural areas is heavily contaminated with nutrients, suspended sediments (due to a lot of erosion upstream) and organic materials whilst from urban areas the predominant pollutants are heavy metals and some nutrients. It was therefore concluded that the Nyabugogo River system is very heavily polluted and urgent action to control both rural and urban pollution is required. Further studies are required to isolate and quantify the sources of this pollution.