Surface water samples were collected from 24 sampling sites throughout the Le’an River during wet and dry seasons. The concentrations of dissolved heavy metals were determined by inductively coupled plasma-mass spectrometry (ICP-MS). The sources of dissolved heavy metals in the Le’an River were investigated based on the seasonal and spatial variations. The results demonstrated that significant seasonality of dissolved heavy metals concentrations were found in the Le’an River, and high concentrations in dry season due to the precipitation dilution effect. Spatially, higher concentrations of selected dissolved heavy metals were distributed in the mining area, which was significantly influenced by mining activities. It was found that sites within the mining area suffered from serious pollution based on the calculated HPI and MPI. According to human health risk assessment, it was indicated that As, Co, and Cd were the major contributors to exposure to local inhabitants. The exposure risks of the adults were less sensitive compared to the children, and oral ingestion was the primary exposure pathway. Multivariate statistical analyses revealed that different groups of heavy metals were characteristics of the disparate source associated with mineral exploration, urban and agricultural activities, and geogenic origins. Hierarchical agglomerative CA grouped all the sampling sites into three clusters based on the data set of exposure risk to human health and aquatic life. In cluster 2, concentrations of Cd and As were higher than drinking water quality of WHO and Chinese standards.