Although the health of rivers is threatened by multiple anthropogenic stressors with increasing frequency, it remains an open question how riverine microbial communities respond to emerging micropollutants. Here, by using 16S rDNA amplicon sequencing of 60 water samples collected during different hydrological seasons, we investigated the spatio-temporal variation and the co-occurrence patterns of microbial communities in the anthropogenically impacted Jiulong River in China. The results indicated that the riverine microbial co-occurrence network had a nonrandom, modular structure, which was mainly shaped by the taxonomic relatedness of co-occurring species. Fecal indicator bacteria may survive for prolonged periods of time in river water, but they formed an independent module which had fewer interactions with typical freshwater bacteria. Multivariate analysis demonstrated that nutrients and micropollutants [i.e., pharmaceuticals and personal care products (PPCPs)] exerted combined effects in shaping α- and β-diversity of riverine microbial communities. Remarkably, we showed that a hitherto unrecognized disruptive effect of PPCPs on the abundance variations of central species and module communities was stronger than the influence of physicochemical factors, suggesting the key role played by micropollutants for the microbial co-occurrence relationships in lotic ecosystems. Overall, our findings provide novel insights into community assembly in aquatic environments experiencing anthropogenic stresses.