Securing the quality and safety of drinking water is an escalating global challenge. A key step in characterizing the risk associated with consuming tap drinking water is comprehensively characterizing the chemical composition of these waters. Without detailed and spatially resolved characterization, linking specific health outcomes to exposure is difficult. Despite this, a growing body of evidence indicates that epidemic diseases can be associated with chronic consumption of contaminated drinking waters. Nontarget analysis (NTA) utilizing high-resolution mass spectrometry offers a broad assessment of the chemical composition of tap drinking waters. We present findings from a 2022 sampling campaign where 12 tap water sources across western Oregon and 1 commercial water source were sampled and analyzed using NTA methods. These water samples were analyzed with multi-modal extraction and chromatographic techniques to target physiochemically polar to non-polar organic contaminants and increase the overall chemical coverage of the water analysis. Over 3,000 unique spectral features were observed, and high confidence chemical annotations were made for over 50 features. Prioritization to select contaminants for further confirmation included rapid toxicity screening achieved through the USEPA’s Cheminformatics Hazard Comparison Dashboard, with hazard profiles revealing potential developmental, reproductive, and carcinogenic risks to humans. A total of 13 compounds were confirmed by reference standard comparison including 5 chemicals of emerging concern. Confirmed water contaminants with little or no prior in-vivo toxicity data were evaluated for toxicity using the zebrafish 215, demonstrating common adverse outcomes in behavioral endpoints and some adverse morphological outcomes. Finally, contaminant mixtures representative of tap water samples were tested for toxicity to more wholistically assess the risk associated with Oregon tap waters. Water contaminants were identified in both analytical extraction and chromatographic methods, demonstrating the value of methods focused on comprehensive contaminant screening. The data presented here, including detections and complementary toxicity data for lesser-known water contaminants, aim to support advancement for the best practices for water quality monitoring, complement ongoing regulatory efforts, and ultimately enhance the quality and safety of public tap water sources.