Decades of industrial activity have designated the lower 10 miles of the Willamette River as a Superfund site since 2000, focusing remediation efforts on metals, dioxins, and polycyclic aromatic hydrocarbons. However, little attention has been given to assessing the variability of emerging contaminants in Portland Harbor. Following requests by the Portland Harbor Community Coalition (PHCC), this study ensured continuous community dialogue and identified six sampling sites to collect water grab samples over 6 months. Samples underwent liquid chromatography high-resolution mass spectrometry analysis, employing suspect and non-targeted analyses to detect emerging contaminants. No distinct differences were observed between sites within and outside the Superfund area, but downstream (Site 6) exhibited notable monthly variations, potentially influenced by its proximity to the Columbia River and a wastewater treatment plant. Temporal variability predominated, with few compounds detected frequently. In most samples, no biological effects were observed with high-throughput zebrafish assays. Combining community engagement, suspect screening, and toxicity testing presents a novel approach to prioritize contaminants for further assessment. These findings inform community groups and regulatory agencies about potential risks associated with emerging water contaminants.