Environmental change, including joint effects of increasing dissolved organic carbon (DOC) and total phosphorus (TP) in boreal northern lakes could potentially affects food web energy sources and the biochemical composition of organisms. These environmental stressors are enhanced by anthropogenic land-use and can decrease the quality of polyunsaturated fatty acids (PUFAs) in seston and zooplankton, and therefore, possibly cascading up to fish. In contrast, the content of mercury in fish increases with lake browning potentially amplified by intensive forestry practises. However, there is little evidence on how these environmental stressors simultaneously impact beneficial omega-3 fatty acid (n3-FA) and total mercury (THg) content of fish muscle for human consumption. A space-for-time substitution study was conducted to assess whether environmental stressors affect Eurasian perch (Perca fluviatilis) allochthony and muscle nutritional quality [PUFA, THg, and their derivative, the hazard quotient (HQ)]. Perch samples were collected from 31 Finnish lakes along pronounced lake size (0.03–107.5 km2), DOC (5.0–24.3 mg L−1), TP (5–118 μg/ L) and land-use gradients (forest: 50.7–96.4%, agriculture: 0–32.6%). These environmental gradients were combined using principal component analysis (PCA). Allochthony for individual perch was modelled using source and consumer δ2H values. Perch allochthony increased with decreasing lake pH and increasing forest coverage (PC1), but no correlation between lake DOC and perch allochthony was found. Perch muscle THg and omega-6 fatty acid (n6-FA) content increased with PC1 parallel with allochthony. Perch muscle DHA (22:6n3) content decreased, and ALA (18:3n3) increased towards shallower murkier lakes (PC2). Perch allochthony was positively correlated with muscle THg and n6-FA content, but did not correlate with n3-FA content. Hence, the quality of perch muscle for human consumption decreases (increase in HQ) with increasing forest coverage and decreasing pH, potentially mediated by increasing fish allochthony.