question: Eight compounds from three categories of pharmaceuticals [5 antibiotics, 2 non-steroidal anti-inflammatory drugs, and 1 anti-epileptics] were monitored at 24 sites in the tributaries of the Han River watershed in South Korea, 2016. The seasonal occurrence, temporal-spatial variation, potential compound source(s), and a risk assessment of this watershed, which is the largest drinking water source in the country, were investigated. Clarithromycin was detected most frequently (72.2%) with the greatest median concentration (0.151 ± 0.072 µg L-1), followed by carbamazepine and sulfamethoxazole. The seasonality of the pharmaceuticals was observed, with higher concentrations and detection frequencies in spring than in summer and autumn; this was possibly caused by lower levels of microbial activities associated with lower water temperatures than other seasons. In terms of geographical variation, urban areas had higher pharmaceutical concentrations than rural areas, which was attributed to the former's high population density and largest wastewater treatment plants (WWTPs) regardless of season. The total concentration and detection frequency of WWTPs were 12.4 and 2.5 times higher in downstream sites than upstream sites, thereby conveying that WWTPs were the main source for the presence of pharmaceuticals in tributaries. According to the results produced from calculations of the risk quotient (RQ) of aquatic organisms, clarithromycin and sulfamethazine were identified as posing relatively high ecological risk (RQ > 1) during the spring that was identified for this study. This study can provide policymakers with scientific support for prioritizing pollutant management and collections of global data on emerging pollutants.