The ubiquitous occurrence and persistence of per- and polyfluoroalkyl substances (PFAS) in all environmental matrices and biota poses significant health risks to humans. Fish consumption is one of the main pathways humans are exposed to PFAS, yet general patterns in factors influencing PFAS content in fish fillets remain unknown. We assembled information on PFAS content (total quantified PFAS, PFOS, PFOA, and others) in fish fillets to assess the effect of fish origin (marine, freshwater, wild, or farmed), fillet type (skin-on or skin-off), and lipid content on PFAS variation across environments at a global scale. We found that these factors influenced PFAS contents in fish fillets, with concentrations reaching up to 2149 ng•g wet mass⁻¹ (WM). Specifically, PFOS and PFOA in skin-off fillets were consistently lower in farmed than wild fish across freshwater and marine environments. In freshwater wild fish, PFOS was lower in skin-off fillets than skin-on fillets at group and species levels, and multiple PFAS showed an inverse relationship with the lipid content of skin-off fillets, though the slopes showed varying steepness depending on the carbon chain length and functional group of the PFAS. However, the high variability of PFAS content across sites in aquatic environments and the complexity of PFAS bioaccumulation mechanisms in fish tissues may lead to variable results at a fine scale (i.e., species level); this highlights general patterns of factors influencing PFAS bioaccumulation that may inform the management of human exposure to PFAS through dietary consumption.