Based on panel dataset of water pollutant emission and socio-economic development in Yangtze River Economic Belt (YREB) during the "Twelfth Five-Year Plan" period, the tempo-spatial evolution and pattern of water pollutants reduction was analyzed. Meanwhile, the spatial effects and driving forces of water pollutant emission reduction were quantitatively estimated by using spatial lag model and spatial error model. Water pollutant emissions reduction presented a significant agglomeration in the YREB, and the high emission-high emission reduction zones were mainly distributed in the Yangtze River Delta. However, the high emission-low emission reduction zones that were being threatened by environmental degradation as the rapid socioeconomic development, still exist, then it was urgent to accelerate the adjustment of industrial structure and the elimination of outdated production capacity, and fully implement the strict controls on emissions by existing standards. The geographical distribution of water pollutant emissions had a significant impact on its reduction in the YREB, namely, increase in water pollutants emission in a place would lead to nonsignificant reduction in water pollutants emission in adjacent areas. However, through exert the environmental control during the "Twelfth Five-Year Plan" period, the trend of coordinated emission reduction emerged since 2015. Population size, the percentage contribution of agriculture in GDP, and urbanization level were the major driving factors behind the variation of water pollutant emissions in the YREB. By 2015, the effects of former two factors worn off, while urbanization still had an increasing influence on the growth of water pollutants emissions. This finding reflected the ongoing urbanization in YREB should be given an urgent attention in the future. In addition, foreign direct investment and industrialization level played a positive role in the increases in chemical oxygen demand and ammonia nitrogen emissions, respectively. In this case, it was necessary to be alert to the rapid FDI inflows and industrialization that may increase the burden of reducing water pollutants emissions. Finally, main policy implications were presented as follows:it was crucial to jointly removing the spillover effect of distribution of water pollutants emissions, and promoting local and their adjacent regions to reach regulatory consensus on pollution standard and total scale. Moreover, establishing deep-level emission reduction models, such as environmental access mechanisms, pollution payment policies, and cross-border early-warning systems, should be constructed and promoted. Besides the implementation of project emission reductions laws and policies, the structural emission reductions should be reinforced. Aiming at the spatial coupling of driving factors and pollution emissions, we should shift the structures of industries, consumption, planting, and capital to the cleaner ones.