River water assessment is needed to establish the potential mitigation regarding the reduction of water quality in the river and estuary, which may affect the production of aquatic life including the blood cockles. Therefore, this research aims to assess the water quality in the Sungai Buloh River and estuary, evaluate the potential risk using the risk quotient (RQ) approach, and determine the mitigation for this problem. The water quality parameters assessed in this research include turbidity, chemical oxygen demand (COD), ammoniacal nitrogen (NH3-N), total dissolved solids (TDS), and the heavy metals zinc (Zn) and copper (Cu). The assessment was carried out from February to June 2022 at eight sampling points along the Sungai Buloh River and a sampling point at the blood cockle farm. The results show that turbidity, COD, NH3-N, and copper exceeded the permittable limit of the Standard Class II National Water Quality Standard (NWQS) of Malaysia. The high loading of these contaminants in the river was possibly sourced from industrial effluents, landfills, and the residential area nearby. The risk quotient (RQ) values indicated there was a high risk of these contaminants harming the river water and blood cockles’ ecosystems at the estuary; meanwhile, TDS and Zn contamination were categorized as moderate risks. The parameters with high RQ values must be mitigated and controlled to prevent a severe and long-lasting impact on blood cockles and other rivers and estuary biotas. The mitigation methods suggested are enforcement of laws and rules, pretreatment of sewage and sewerage before discharging, reforestation, installation of erosion-preventive structures (gabion and stone walls, erosion blankets, sandbags), and installation of a water quality monitoring station and multistage water treatment plant.