Artisanal small-scale mining has been part of Ghana's history, but recent public outcry on the devastating impacts of the phenomenon on water bodies, due to expansion in the sector, has led to clamp downs by various governments on the activity. This has called for evaluation of the water quality of the South-western Rivers System, which are small-scale mining endemic areas. Thirty-five river samples were collected in July 2018 and were analyzed for physico-chemical parameters using procedures outlined in the Standard Methods for the Examination of Water and Wastewaters. The results revealed that the rivers are polluted with Fe and Cu, accompanied by very high levels of turbidity (mean = 488 NTU) and total suspended solids (TSS) (mean = 382mg/L). NH3-N, PO4-P, BOD, and DO levels indicated mild pollution in the waters. Pollution of the rivers is attributable to impacts of artisanal small-scale mining, surface run-off as a result of high intensity rainfall, anthropogenic (indiscriminate waste disposal) and geogenic factors such as dissolution of minerals from the soil zone. It was observed that, if not strictly regulated, turbidity and TSS levels arising mainly from illegal small-scale mining activities could lead to shutdowns of a number of Ghana Water Company Limited treatment plants, leading to water supply challenges in the study area.