17 perfluorinated compounds (PFCs) were systematically investigated in the surface water from principal watersheds of Shanghai, China. 10 PFCs were above the detection limit (0.08–0.28 ng/L) in 39 surface water samples. The perfluorooctanoic acid (PFOA) and perfluorobutanesulfonate (PFBS) were the two dominant compounds with a median concentration 50.67 ng/L and 29.84 ng/L, respectively. Concentrations of perfluorooctanesulfonate (PFOS) were generally less than PFBS, which might result from the global phase-out of PFOS production and the use of PFBS as a substitute for PFOS-based products. There were three major polluted areas of PFOA along the Huangpu River. The PFOA concentration in groundwater samples collected from one of the three areas indicated that chemical industry might be the possible source. The perfluoroalkane sulfonates (PFSAs) level had a spatial trend that indicated northwest had higher concentrations than the southeast. The distribution of PFCs was not much affected by atmospheric deposition. Mass loading analysis in the surface water revealed that the Huangpu River exhibited relatively large mass loading of total PFCs of 1742.43 kg/year to Yangtze River Estuary. The predominant of the PFC species was PFOA with 652.65 kg/year. The current concentrations of PFOA and PFOS were at middle level comparing to other studies in China and worldwide. Risk assessment of 6 PFCs showed that there is no risk to the aquatic organisms in Shanghai. PFOS and PFBS had low risk to the avian. Furthermore, the adults living in Shanghai were at low risk to exposure to PFCs through water consumption.