Economic production activities have led to a series of environmental problems in many countries around the world. In this study, a multi-scenario ensemble simulation and environmental input-output (MES-EIO) model is developed for analyzing the impacts of different behaviors/policies over various economic sectors and generating the desired schemes of mitigating multi-pollutant emissions. MES-EIO is not only capable of simulating environmental emissions over a long-term planning horizon, but also describing the impacts of complex economic system on multi-pollutant and carbon dioxide (CO₂) emissions. The MES-EIO model is also applied to a real case of Guangdong province (in China) to display its applicability in environmental-emission simulation, where multiple scenarios are designed to examine the effects of different system components on modeling outputs. The major findings are: (i) agriculture, manufacturing and energy production would be the main environmental emission sectors over the planning period; (ii) through ensemble simulation, it could be noted that emissions of chemical oxygen demand (COD), ammonia nitrogen (NH₃–N), sulfur dioxide (SO₂) and nitrogen oxide (NO_x) would decrease by [17.6%, 60.7%], [14.7%, 59.3%], [28.3%, 63.4%] and [29.7%, 64.1%] during 2020–2030; (iii) rapid economic development may lead the city encounter the risk of severe environmental pollution, while low economic growth could not meet the demand of population expansion and urbanization; (iv) according to the results of scheme analysis, scenario S_2-3-1 (followed by scenario S_2-2-1) would be optimal for supporting sustainable development within the study area. The findings are helpful for generating optimized emission-reduction schemes that can effectively balance the tradeoff between socioeconomic development and environmental conservation.