Although heterotrophic prokaryotes (HP) play a crucial role in biogeochemical carbon cycles, microbial oceanographic studies associated with heavy precipitation-induced large-scale freshwater runoff are understudied in the East China Sea (ECS), the largest continental shelf in the northwest Pacific. To elucidate the impact of Yangtze River Diluted Water (YRDW) on HP production (HPP) and growth-limiting resources, we conducted comprehensive microbial oceanographic measurements in combination with analysis of satellite images and optical property analyses of dissolved organic carbon (DOC) over three consecutive years in the northern ECS. Our results revealed that the HPP and chlorophyll-<em>a</em> were consistently highest in summer due to the supply of excess DOC and nutrients via YRDW, which is intriguing considering the enhanced HPP coupled with spring phytoplankton bloom in middle latitudes in general. However, the exceptionally great YRDW runoff induced by heavy rainfall resulted in excessive supply of terrestrial-origin recalcitrant DOC and nutrients imbalance with high N:P ratio (34), which was responsible for the limited DOC bioavailability and phosphorus-limitation for the HPP. Accordingly, the enhanced HPP to primary production ratio (> 0.5) in summer suggested enhanced carbon flow via microbial loop, which ultimately affects fishery structure and production by reducing energy efficiency in food web process. Our results demonstrating the contrasting impact of YRDW on regulating (i.e., either stimulating or suppressing) the HPP provide new insights into the microbial responses to climate change-induced large-scale freshwater discharge, which is applicable to other ocean basins receiving great freshwater inputs (e.g., Amazon River and Arctic Ocean) accompanied by increasing precipitation.