Ten nonsteroidal antiinflammatory drugs (NSAIDs), two blood lipid regulators (BLRs), and two antiepileptic drugs (AEDs) were analyzed in the Pearl River system in China (i.e., Liuxi, Zhujiang, and Shijing Rivers) and four sewage effluents during the dry and wet seasons, and the environmental risks they posed were assessed. Eight pharmaceuticals were detected in the rivers and effluents, including five NSAIDs (salicylic acid, ibuprofen, diclofenac, mefenamic acid, and naproxen), two BLRs (clofibric acid and gemfibrozil), and one AED (carbamazepine). The median concentrations for the eight pharmaceuticals ranged from 11.2 to 102 ng/L. Seasonal variations were not obvious for most pharmaceuticals in the three rivers, except for salicylic acid and clofibric acid in the Zhujiang River, and diclofenac in the Zhujiang and Shijing Rivers. However, spatially considerable variations in the concentrations were observed for the eight pharmaceuticals in all three rivers. For most of the pharmaceuticals, the effluents from the four wastewater treatment plants and Shijing River water were found to be the major discharge sources for the Zhujiang River, but with additional discharge sources from some small urban streams in the wet season. Diclofenac in the Shijing River was the only pharmaceutical that had a risk quotient (RQ) >1, indicating a high risk to aquatic organisms in the river. Although higher RQs were calculated for the mixture of the pharmaceuticals in each river, the risk rating remained the same for the three rivers with the RQ being >1 only in Shijing River.