Perfluorinated chemicals (PFCs) have been detected in abiotic and biotic matrices worldwide, including the Arctic Ocean. Considering these chemicals’ persistent and bioaccumulative potentials, it was expected that levels of PFCs, like those of many legacy organic pollutants, would respond slowly to the restrictions in production and usage. Temporal trend studies in remote areas, such as the Arctic, can help determine the chronology of contamination and the response of the environment to regulations on PFCs. Prior to this study, temporal trends of PFCs in Alaskan coastal waters had not been examined. In the present study, concentrations of six PFCs were determined in livers of northern sea otters (Enhydra lutris kenyoni) collected from three areas in south-central Alaska (Prince William Sound, n = 36; Resurrection Bay, n = 7; Kachemak Bay, n = 34) from 1992 to 2007. Additionally, previously published profiles and concentrations of PFCs in southern sea otters from California and Asian sea otters from Kamchatka (Russia) were compared to our new data, to determine the geographical differences in PFC profiles among these three regions in the Pacific Ocean. Perfluorooctanesulfonate (PFOS), perfluorooctanesulfonamide (PFOSA), and perfluorononanoate (PFNA) were the predominant PFCs found in the livers of northern sea otters from 1992 to 2007. Other PFCs, such as perfluorooctanoate (PFOA), perfluoroundecanoate (PFUnDA), and perfluorodecanoate (PFDA), were detected less frequently, and at low concentrations. Overall, from 2001 to 2007, a decrease in concentrations of PFOS was found in northern sea otters, suggesting an immediate response to the phase-out in 2000 of perfluorooctanesulfonyl-based compounds by a major producer in the United States. In contrast, concentrations of PFNA in northern sea otters increased by 10-fold from 2004 to 2007. These results indicate that the contribution by PFNA to ΣPFC concentrations is increasing in northern sea otters. The profiles (i.e., composition of individual PFC to ΣPFC concentration) of PFCs in northern sea otters from Alaska were similar to those reported for southern sea otters from California, but were considerably different from the profiles reported for Asian sea otters from Russia, suggesting differences in point sources of exposure.