The control of multiple pollutants from non-point sources is very difficult because their loss potentials are not consistent on the same spatial distributions. In this research, an innovative approach was established for multiple-pollutant priority management areas (MP-PMAs). In the new framework, the MP-PMA approach focused on the sensitive areas that contributed a variety of pollutants instead of a specific targeted pollutant by integrating a watershed model and a Pareto-based multi-criteria evaluation approach. Based on the results, multiple levels of MP-PMAs were established with respect to the corresponding requirements of clean water statutes. Compared to traditional separate strategies, the MP-PMA approach would lead to more cost-effective watershed management because those moderate-level PMAs for specific targeted pollutant might be the high-level MP-PMAs. With respect to spatial distribution, the MP-PMA approach provided more accurate target results for the high-level PMAs, especially among the headwater areas. From a scientific view, the MP-PMA approach provides an integrated suggestion for the placement and removal potentials of best management practices at the watershed scale. (C) 2014 Elsevier B.V. All rights reserved.