This research aimed to improve our understanding of the sources of micropollutants in the Hudson River Estuary. We collected samples from seventeen locations along the Hudson River Estuary during May, July, and September 2016. The sample locations were selected to target sewage treatment plant (STP) outfalls and tributaries that are expected to be major sources of micropollutants in the Hudson River. The samples were analyzed to quantify the occurrence of 200 wastewater-derived micropollutants and pesticides. The data was analyzed to identify the relative contributions of various sources of micropollutants and specific outfalls or tributaries that are sources of micropollutants in the Hudson River Estuary, and revealed four distinct clusters of micropollutants grouped by their occurrence profiles. Rondout Creek and Normans Kill were both identified as major contributors of wastewater-derived micropollutants to the Hudson River Estuary. Rondout Creek was also identified as a major contributor of agricultural micropollutants. Our geospatial analysis revealed several associations between the spatiotemporal occurrence clusters and certain geographic catchment features including the extent of total agricultural land cover, extent of cultivated cropland land cover, number of major STP outfalls, and hydraulic distances to major STP outfalls. These data can be used to develop targeted micropollutant mitigation strategies in the Hudson River Estuary.