Heavy metal pollution from both anthropogenic and natural processes can have significant effect on environmental quality of stream and river systems. However, in Ghana, heavy metal pollution of waterbodies is attributed mainly to mining activities but the role of natural mechanisms in altering stream water and sediment quality in relation to heavy metals has received little attention. Spatial and temporal variation in water quality parameters and heavy metal concentrations in water and sediments were studied comparatively in a river and two streams in a gold-rich watershed impacted by heavy mining activities. Samples were collected monthly over a twelve-month period from November 2010 to October 2011 from upstream (unmined) and downstream (mined) sections of the studied streams. Parameters measured include temperature, dissolved oxygen, conductivity, pH, turbidity, colour, mercury (Hg) and arsenic. High spatial variability of water quality parameters was found. Hg concentrations in water were extremely low in both upstream and downstream areas. Maximum geochemical background levels of Hg in unmined pristine areas were 2.45 mg/g whilst arsenic was 29.10 mg/g. By contrast, gold-mined downstream areas recorded Hg and arsenic concentrations of 8.75 mg/g and 82.53 mg/g in stream sediments respectively. Levels of Hg and arsenic in sediments were several orders of magnitude greater than concentrations in surface water in downstream sections and this may be explained by substances originating from mining activities, upstream transport or remobilized sedimented materials in the overlying water column. Our study showed that both natural and human activities may contribute to heavy metal pollution in the highly mineralized watershed of the Pra River Basin. Human factors are however likely to amplify the natural background levels of heavy metals