Nowadays, routine water quality assessment approaches are replaced by integrated monitoring and management of water resources. In this content, models are one of the management tools that are available and can be useful for managers and decision makers. Regarding this fact that models can be run for different scenarios after their setup, they can used to decrease economic costs of large projects. Zayandehrud River is the lifeline of Isfahan province at the central part of Iran and is an important water source for drinking, industries and in particular irrigation of agricultural fields. Therefore, water quality assessment of this river is one of the most important issues to water management of Zayandehrud River. This study used WASP model to simulate concentration of cadmium (Cd) and lead (Pb) heavy metals in the water and sediments of Zayandehrud River. So, 12 water and sediment samples were collected from Zayandehrud River at 3 temporal periods from 10 stations along the river and 2 samples were collected from 2 important drains that bring in pollution to the river. All samples were analyzed using flame and graphite furnace atomic absorption spectrometry immediately after taking to laboratory. The results showed that average concentration of Pb and Cd in water samples was 0.015 and 0.083 mg/L, respectively. With regard to the national standards of Iran (limits are 0.05 mg/L Pb in potable water, and 0.05 mg/L Cd in irrigation water), Pb concentration of water is in the range of standards and there isn’t any concern about it, but Cd concentration is higher than irrigation water standard that is hazardous . Average concentration of Pb and Cd in sediment samples was 39.5 and 9.16 mg/kg, respectively. Both Pb and Cd concentration in the sediments is higher than average earth’s crust concentration which shows the presence of anthropogenic pollution resources in the study area. Results also revealed that anthropogenic pollution sources introduce Cd to the river, besides geological effect of the watershed. Muller index showed that river sediments are polluted by Cd and Pb and management options should take place to decrease heavy metals concentration in the water and sediments of Zayandehrud River. Model precision and sensitivity was assessed using RMS error. Discharge simulation precision was 9% that is acceptable and shows good precision. Cadmium concentration simulation error was 0.02 that is very good precision of the simulation. Lead concentration simulation precision was 9% but the model can’t simulate Pb concentration and trend in the river water. Probably, this is due to behavior and low concentration of Pb in the aqueous environments. Thus WASP model needs more data for simulation of behavior and concentration of Pb in the river. Key Words: Zayandehrud, Heavy metals, WASP model, Water quality, Lead, Cadmium