Heavy metal pollution is one of the important threats to river water quality and human health. Here, we collected surface water samples from the mainstream and tributaries in the Ganjiang River basin in January and July, 2015, in order to delineate the temporal-spatial distribution characteristics of heavy metals, identify their sources, and assess their potential risk. Compared with China’s environmental quality standards for drinking water, our results revealed that 5 heavy metals, including Fe, Al, As, Mn and Tl, exceeded the standard values and the over-standard rates were 21.62%, 16.22%, 8.11%, 4.05% and 4.05%, respectively. The concentrations of hydrochemical ions and heavy metals exhibited significant seasonal variation and spatial heterogeneity. Multivariate statistical approaches indicated that intense anthropogenic activities (mining industries and agricultural activities) were the most important sources of heavy metals in the Ganjiang River, and the upstream of the Ganjiang (in southern Jiangxi Province) and the Yuan River were the regions with the most serious pollution. Assessming health risk using the hazard index (HI) and carcinogenic risk (CR) recommended by the USEPA showed that children were more susceptible to the health risk than adults, and As was the most largest contributor leading to noncarcinogenic and carcinogenic risk to human health. Therefore, effective measures such as controls on mining wastewater and the use of pesticides and fertilizers should be taken by local government to protect aquatic ecosystems and human health.