Over-fertilization and straw returning were the vital issues that restrict the sustainable development of agricultural ecosystems in China. In this study, a process-based biogeochemical model-DNDC was adopted to simulate carbon (C) and nitrogen (N) loss from rice-wheat rotation system under different fertilization and straw returning measures, and then identify the best management practice in rice-wheat rotation system in Shanghai. The results indicated that reducing fertilization and straw returning could significantly impacts N loss, greenhouse gas (GHG) emissions and soil C storage in rice-wheat rotation ecosystem. Reducing fertilization by 25% combined with straw returning (75%CK+SR) was identified as the best management practice in rice-wheat rotation ecosystem by DNDC model, which could significantly reduce N loss by 41.67% and reduce N₂O emissions by 51.85%, respectively, while maintained the best rice yields. Straw returning would increase CH₄ emissions from rice-wheat rotation ecosystem, while significantly enhanced soil C storage. In addition, reducing fertilization by 50% (50%CK and 50%CK+SR) would lead to rice yields reduction by 3.06%~9.90%. Compared with traditional practice (CK), the identified best management (75%CK+SR) could efficiently improve ecological environmental benefit in the rice-wheat rotation. The results also provides reference for the control of C and N loss in the rice-wheat rotation in China.