To understand the further impacts of multiple stressors in freshwater, we investigated the effects of heavy metal (HM, Cu and Zn) and nutrient enrichments (nitrogen and phosphorus, NP) on microbial decomposition of Pterocarya stenoptera litter and the associated extracellular enzyme activities and microbial biomass with microcosms. Results showed that the decomposition rates were slower in the polluted stream waters than those in the unpolluted ones, which corresponded to lower microbial biomass and integrated enzyme activities of cellulose and β-glucosidase. The decomposition rates were accelerated at low HM level, which was associated with the stimulated enzyme activities of hydrolytic enzymes or was stimulated by both NP levels in polluted stream waters. In particular, the hydrolase enzyme activities of microbial communities in polluted stream waters were stimulated by low HM level, suggesting that low HM level-stimulated litter decomposition may be due to the increased enzymatic activities. When microbial communities were exposed to HM and NP simultaneously, the inhibitory effect (in unpolluted stream waters) or the stimulated effect (in polluted stream waters) of low HM concentration was enhanced and attenuated, respectively, which suggests that the NP antagonistic effect against HM toxicity on litter decomposition may contribute to the litter-associated extracellular enzyme activities. These results suggest that the co-occurrence of HM and NP may have antagonistic effects on stream ecosystem functioning.