Due to the acceleration of industrialization and urbanization in recent decades, the majority of coastal rivers and estuaries in China have been moderately or severely contaminated by a variety of pollutants. We investigated the spatial and seasonal variations of water nutrients (permanganate index, chemical oxygen demand, biochemical oxygen demand, ammonium, nitrate, total nitrogen, and total phosphorus) and heavy metals (Hg, Pb, Cu, Zn, Se, As, Cd, Cr, Fe, and Mn) in 27 subtropical rivers draining into the South China Sea. Our results indicated that the average concentrations of all water quality parameters except ammonium, total nitrogen, and total phosphorus satisfied the requirements for grade III of the surface water quality standard of China. The concentrations of both nutrients and heavy metals showed a strong spatial variation. Cluster analysis classified the 27 rivers into three spatial clusters corresponding to low, moderate, and high pollution levels. In terms of seasonal variation, the values of chemical oxygen demand and biochemical oxygen demand in wet seasons were significantly lower than those in dry seasons. Multivariate statistical analyses demonstrated that river nutrients might mainly originate from domestic, industrial, and agricultural wastewaters, while heavy metals likely came from industrial activities and natural weathering processes. The findings of this study suggest that for reducing the pollution of subtropical rivers draining into the South China Sea, further efforts should be made to control nitrogen and phosphorus export from catchments.