Air pollution is an increasingly critical health issue responsible for numerous diseases and deaths worldwide. In China, to address severe air pollution in the Yangtze River Delta region, the local government has formulated Five-Year Plans to set the road map for air pollution control by phased targets in 2020, but the effectiveness of these policies is still uncertain. There is therefore a need for accurate prediction of control strategies. Here we present a computational evaluation of the predicted effectiveness of four emission control strategies: normal or enhanced emission reduction for industry and power plants, and normal or enhanced emission reduction for industry, power plants and transportation, designed on the basis of policies of the 13th Five-Year Plans. Effectiveness was tested on concentrations of PM2.5, e.g., particulate matter with aerodynamic diameter less than 2.5 μm, using the two-way coupled Weather Research and Forecasting—Community Multiscale Air Quality (WRF-CMAQ) model. Results show that by implementing the four emission control strategies, only Hangzhou with the strictest emission controls in four main cities (Hangzhou, Hefei, Nanjing and Shanghai) can meet the 20% reduction goals of PM2.5 concentrations in the 13th Five-Year Plan, indicating that current policies are not sufficient to control the severe air pollution in the Yangtze River Delta region. Sensitivity tests show that residential emissions have the highest contributions to the PM2.5 concentrations in January in the four main cities of Hangzhou, Hefei, Nanjing and Shanghai, followed by agriculture, industry, transportation and power plants. Predicted annual mean reduction percentages for PM2.5 are the highest in Hangzhou, from − 9.7 to − 20.1%, followed by Nanjing, from − 8.2 to − 18.7%, Shanghai, from − 7.4 to − 15.8%, and Hefei, from − 6.1 to − 13.8%. This finding highlights the predominance of residential emissions, which should be better controlled, notably coal burning. By comparison, predicted annual contributions of regional transport and natural sources to mean PM2.5 concentrations in four cities range from 29.2 to 36.6%. Overall, a major finding is that residential sources are of comparable importance to industrial, power plant and transportation sources to PM2.5 concentrations, especially for winter. This information will help governments of other regions of China, as well as other developing countries, to formulate more appropriate emission control strategies where coal is used for heating and cooking purposes in the developing countries.