Endocrine-disrupting compounds (EDCs) constitute a wide variety of chemistries with diverse properties that may/can pose risks to both humans and the environment. Herein, a total of 26 compounds, including steroids, flame retardants, and plasticizers, were monitored in three major and heavily urbanized river catchments: the R. Liffey (Ireland), the R. Thames (UK), and the R. Ter (Spain), by using a single solid-phase extraction liquid chromatography-mass spectrometry (SPE-LC-MS/MS) method. Occurrence and frequency rates were investigated across all locations over a 10-week period, with the highest concentration obtained for the flame retardant tris(2-chloroethyl) phosphate (TCEP) at 4767 ng∙L−1 in the R. Thames in Central London. Geographical variations were observed between sites and were partially explained using principal component analysis (PCA) and hierarchical cluster analysis (HCA). In particular, discrimination between the R. Ter and the R. Thames was observed based on the presence and concentration of flame retardants, benzotriazole, and steroids. Environmental risk assessment (ERA) across sites showed that caffeine, a chemical marker, and bisphenol A (BPA), a plasticizer, were classified as high-risk for the R. Liffey and R. Thames, based on relative risk quotients (rRQs), and that caffeine was classified as high-risk for the R. Ter, based on RQs. The total risks at each location, namely ΣRQriver, and ΣrRQriver, were: 361, 455, and 723 for the rivers Liffey, Thames, and Ter, respectively. Caffeine, as expected, was ubiquitous in all 3 urban areas, though with the highest RQ observed in the R. Ter. High contributions of BPA were also observed across the three matrices. Therefore, these two compounds should be prioritized independently of location. This study represents a comprehensive EDC monitoring comparison between different European cities based on a single analytical method, which allowed for a geographically independent ERA prioritization to be performed.