Ongoing chemical development in response to regulation of historical perfluorinated compounds, (i.e., perfluorooctanoic acid (PFOA) and perfluorooctanesulfonic acid (PFOS)) has resulted in a proliferation of novel per- and polyfluorinated species. Screening and monitoring for these emerging chemicals benefit from a nontargeted approach due to a lack of necessary standards and a paucity of information about the replacement chemistries. In this paper, we apply nontargeted screening to the Cape Fear River of North Carolina, a fluorochemically impacted watershed. The continued presence of perfluorinated ether acids was confirmed, with a total of 37 unique chemical formulas comprising 58 isomers detected. Structural determination was carried out by LC-MS/MS to determine isomeric structures where possible. Novel structures determined included perfluorinated ether acid species containing two acidic sites, polyfluorinated ether acids containing a single hydrogenation, and previously unreported perfluorinated ether acids. Compounds identified by an initial nontargeted screen were monitored over repeated sampling to track long-term reductions in PFAS content during emission source control. Hierarchical clustering of the time course data was used to associate groups of chemicals based on their trends over time. Six clusters were identified and showed some similarity in chemical class; they are believed to represent the byproducts of different fluorochemical production lines.