Pharmaceuticals vastly consumed by modern human for health and food might track anthropogenic impacts on aquatic ecosystem via their wide residual spectrum. This study investigated the spectrum of pharmaceutical residuals in stream water at confluence point of each subwatershed with various land use pattern in Jiulong River watershed, southeastern China. Stream water was sampled in both wet and dry seasons of 2016. Results showed that 59 out of the selected 94 compounds from 6 pharmaceutical categories were quantified among these stream water samples, up to 1488 ng L^-1 for caffeine (CAF). Antibiotics and central nervous system drugs (CNs) collectively dominated the quantified instream pharmaceutical residuals. Outbreaks of epidemic infectious diseases for human and livestock partially but significantly matched seasonality of instream pharmaceutical residuals. Anthropogenic impact as land use composition of subwatersheds was significant on instream pharmaceutical loadings, especially urban land use. Cocktail risk of instream pharmaceutical residuals to aquatic organisms was assessed ranging from low to medium among the subwatersheds except high risk for the W-01 subwatershed in the dry season. Evidence from this study indicated that seasonality and wide spectrum of instream pharmaceutical residual determination could reveal anthropogenic impacts to aquatic ecosystem, such as epidemic disease and land use.