A biogeochemical model is used to simulate the sea-to-air flux of dimethylsulfide (DMS) in the Eastern China Marginal Seas (ECMS) for the period 2011 to 2015. Seasonal and inter-annual variability of sea surface temperature (SST), cloud cover (CLD), wind speed (WIND) and mixed layer depth (MLD) are analyzed. SST peaked in August and displayed a north to south gradient. CLD is around 60% and WIND is within the range 5–11 m/s. MLD ranges from 17m in summer to more than 149m in March. CHL and DMS surface concentration peaked near the Changjiang River mouth during summer. DMS field data was collected by the Ocean University of China (OUC). These data are used together with a genetic algorithm (GA) technique to calibrate both CHL and DMS related key model parameters. Simulated DMS concentrations and DMS flux reach a maximum of 6.1 nM in May and 8.8 μmol m−2d−1 in the middle of July respectively. CMIP5 experiment archive is used to provide physical forcings for the simulation under 4 × CO2 climate conditions. Compared with contemporary climate conditions, under 4 × CO2, annual mean SST increases 19%; WIND decreases 24%; MLD decreases 7.8%. DMS decreases by 25%, and DMS flux decreases by 38%. The change in DMS flux is most likely due to the significant increase of SST and decrease of wind speed. The projected decrease in MLD is likely caused by projected more precipitation in the region leading to increased fluvial discharge and a decrease in salinity under warming.