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Human consumption of pharmaceuticals leads to continuous emissions of active pharmaceutical ingredients (APIs) to the aquatic environment, primarily via wastewater treatment plants (WWTPs). However, temporal and spatial patterns of environmental API concentrations are challenging to assess using conventional chemical measurements. Chemical risk assessments are, consequently, typically based on low-resolution data and often overlook API concentrations of environmental concern. We, therefore, developed a new method, combining emission and hydrodynamic modeling to estimate spatiotemporal variations. The method was applied in a case study in a Swedish lake receiving water from a WWTP (capacity 200,000 person equivalents), including >500 prescription APIs. The emission model was validated using ten different APIs measured monthly in the WWTP effluent, and of 103 measured API concentrations 102 were predicted within a factor of 10. The full method was validated against 321 historical measurements from the lake, covering 20 different APIs where 233 (73%) and 319 (99%) of the predicted concentrations were within a factor of 10 and 100 of the measurements. Thus, our method enables predictions of environmental concentrations of APIs, accurate enough to supplement and guide environmental monitoring, directly from human prescription data. Furthermore, we demonstrate that API concentrations vary by orders of magnitude over time and space, directly impacting risk management and monitoring.