Illegal mining and inappropriate use of agrochemicals have exacerbated surface water pollution in Ghana. The quality of water has changed, and knowledge of their current condition is important for formulating policies to conserve the country’s water bodies. This study assessed the quality of surface waters in Ghana’s Pra River Basin. A survey of 344 local farmers randomly sampled was conducted and a physicochemical analysis of 33 water samples collected from 25 rivers in the basin. Boreholes are the main source of drinking water for 85% of farmers, and they assessed water quality by its appearance. Rainwater provides over 50% of the water needed by the respondents for domestic use. River water was mainly used for crop production and only secondarily for domestic use. At more than 80% of the sampled sites, pH, Fe and P were above the WHO recommended values, while Pb was exceeded at 30% of the sites. Cu, Hg, As and Fe were above permissible levels for irrigation, especially near the mining areas. The poor quality of river water makes it unusable despite its availability. A more effective and efficient land-use policy focusing on buffer zone protection is recommended to minimise water quality degradation in the basin.