Climate-smart agriculture management practices such as no-tillage (NT) and cover crops (CCs) have been widely applied and are expected to offer multiple environmental benefits (e.g., soil carbon sequestration, yield stability, and climate resilience). However, the long-term effects of these management practices, especially their synergistic interaction, have not been well addressed. This study used an improved agroecosystem model (DLEM-Ag) to explore the synergistic effects of NT and CCs on soil carbon dynamics in a continuous maize system in the middle south of the United States for 1970–2099. Simulation results for 1970–2018 show that NT, relative to conventional tillage (CT), led to carbon gains (0.22 Mg C ha−1 yr−1) in the topsoil in a CC-inclusive continuing maize system; however, NT per se brought minor net carbon gains. This well captures the field observations. Model factorial analyses reveal that soil carbon sequestration was highly correlated with biomass carbon inputs from both the winter cereal CC and the summer maize. Elevated CO2 and warming effects were the main contributors to soil carbon gains, as these promote CC growth. Further model projections suggest that soil organic carbon would increase in the RCP 8.5 future scenarios (2019–2099), with greater gains under NT-CCs than under CT-CCs (0.089 vs. 0.058 Mg C ha−1 yr−1), largely due to enhanced CC biomass production. Moreover, NT-CCs would reduce carbon loss compared to CT-CCs (-0.002 vs. -0.017 Mg C ha−1 yr−1) in the RCP 2.6 scenarios. Our study highlights the importance of CCs in enhancing cropland carbon sequestration and indicates that NT and CCs, taken together, can serve as a viable strategy to ensure crop production through promoting soil health in similar maize cropping systems.