Micropollutants in water environments have attracted widespread attention, but how human and natural stressors influence the risks of micropollutants has not been comprehensively revealed. A megacity-scale study of the ecological risks of micropollutants in the surface water of Beijing, China is presented to illustrate the magnitudes of the influences of multiple anthropogenic and natural stressors. A total of 133 micropollutants representing typical land use patterns in Beijing, were quantified with the mean concentration range of ND (not detected) to 272 ng·L−1. The micropollutant concentrations in the south were obviously higher than those detected in the northern areas, and neonicotinoid pesticides showed the highest mean concentration of 311 ng·L−1. The chronic and acute risks of micropollutants to algae, invertebrates, and fishes were determined, and herbicides, organophosphorus esters, and insecticides account for the primary risks to algae, invertebrates, and fishes, respectively. The cropland and impervious cover cause the differences in the pollution and risks of micropollutants. The land use in riparian zones greater than 2 km shows a great influence on the chronic chemical risks (CCRs) for the three groups of species, indicating that too local scale does not explain the local pollution status. Climate conditions and human land use are important drivers explaining the CCRs to which various trophic levels of species are exposed. Results demonstrate that multiple categories of micropollutants pose adverse risks to freshwater in the megacity of Beijing, while climate conditions, pollution discharge, and human land use induce the chemical risk of micropollutants to aquatic organisms, and the land use in different riparian zones show different effects on the risks.