AbstractThe frequency of riverine floods is predicted to increase in East Asia. However, the response of coastal hypoxia (<63 μmol L−1) to floods has not been well understood. In the summer of 2020, characterized by one of the most significant Changjiang water fluxes in three decades, we conducted a cruise during the flood period on the East China Sea inner shelf. Our observations revealed severe bottom hypoxia with a maximum spatial coverage of ∼11,600 km2 and a minimum dissolved oxygen concentration (DO) of 21 μmol L−1. In the surface layer, the relationships between salinity and nitrate, dissolved inorganic carbon (DIC) indicated significant organic matter production, validated by a high‐Chlorophyll‐a (Chl a) patch (>5 μg L−1). Furthermore, the significant relationship between apparent oxygen utilization and DIC of deep waters reveals that the organic matter decomposition primarily drove the hypoxia during the flood period. Episodic wind events also influenced bottom DO and DIC, by transporting surface waters to the deep. Multiple‐years data set shows that the average Changjiang nitrate flux during flood years is about 1.4 times that during non‐flood years. The flood waters mix with estuarine waters, forming the high‐nutrient plume waters, which expanded farther offshore during the flood period. While high turbidity remained confined to the inner estuary. Consequently, the high‐Chl a area significantly expanded, which significantly exacerbated the hypoxia.