A major source of toxic per- and polyfluoroalkyl substances (PFAS) is aqueous film-forming foams (AFFF) used in firefighting and training at airports and military installations, however, PFAS have many additional sources in consumer products and industrial processes. A field study was conducted on fish tissues from three reaches of the Columbia Slough, located near Portland International Airport, OR, that are affected by AFFF and other PFAS sources. Fishes including largescale sucker (Catostomus macrocheilus), goldfish (Carassius auratus), and largemouth bass (Micropterus salmoides) were collected in 2019 and 2020. Fish blood, liver, and fillet (muscle) were analyzed for target and suspect PFAS by liquid chromatography high resolution mass spectrometry (LC-HRMS). Data were analyzed for patterns by fish species, tissue type, and river reach. Thirty-three out of 50 target PFAS and additional suspect compounds were detected at least once during the study, at concentrations up to 856 ng/g. Seven carboxylic acids (PFOA, PFNA, PFDA, PFUdA, PFDoA, PFTrDA, PFTeDA), three sulfonates (PFHxS, PFOS, PFDS), three electrofluorination-based compounds (FBSA, FHxSA, FOSA), and two fluorotelomer-based compounds (8:2 FTS, 10:2 FTS) were the most frequently detected compounds in all tissue types. The C6 (PFHxS) to C10 (PFDS) homologs were detected with PFOS and FHxSA at concentrations 1–3 orders of magnitude greater than the other PFAS detected. This is the first report of Cl-PFOS, FPeSA, and FHpSA detected in fish tissue. In all fish samples, fillet concentrations of PFAS were the lowest, followed by liver, and blood concentrations of PFAS were the highest. Differences in PFAS concentrations were driven primarily by tissue types and to a lesser extent fish species, but weakly by river reach. The Oregon Health Authority modified an existing fish consumption advisory on the Columbia Slough to recommend no whole-body consumption of most fish to avoid elevated levels of PFOS in fish liver. Measured PFAS concentrations in fish tissues indicate the potential for adverse ecological effects.