The implementation of the extended producer responsibility (EPR) for e-waste is an important measure to develop an ecological civilization. In order to advance manufacturing enterprises to effectively implement resource and environmental responsibility, this study investigates the main causes of environmental regulation failure from the perspective of government and enterprises. The game theory was used to establish an evolutionary game model between government regulatory departments and electronic and electrical products’ manufacturing enterprises. A system dynamic model was utilized to construct the stock-flow graph of the game between government and enterprises, and to carry out simulation analysis under different strategies. The results found that the probability of an enterprise undertaking extended responsibility gradually increased and stabilized with the increase of government supervision and punishment intensity; the government’s regulatory probability and punishment are important factors affecting the enterprises’ compliance with regulations and responsibilities. The study suggests that government should focus on strengthening environmental regulations from the aspects of improving laws and regulations, establishing a regular monitoring system and innovating incentive and constraint mechanism.