The coastal region in east China experiences massive anthropogenic eutrophication, and the bottom water off the Changjiang River Estuary in the East China Sea faces the threat of severe seasonal hypoxia. We find that projected future climate changes will work in parallel with anthropogenic eutrophication to exacerbate current hypoxia and increase shelf vulnerability to bottom hypoxia. We use a coupled physical-biogeochemical regional model to investigate the differences of shelf hydrography and oxygen dynamics between present and future projected states. Model results indicate that the Yellow Sea Cold Water Mass which plays essential roles in nekton migration and shellfish farming practically disappears by the end of the 21^st century, and shelf vertical stratification strengthens by an average of 12.7%. Hypoxia off the Changjiang River Estuary is exacerbated with increased (by one month) hypoxia duration, lower dissolved oxygen minima, and significant lateral (202%) and vertical (60%) expansions of hypoxic water. Reduced oxygen solubility, and accelerated oxygen consumption under increased primary production and rising water temperature contribute 42% and 58%, respectively, of bottom dissolved oxygen decrease in the East China Sea. Model results also show increased vertical diffusion of oxygen, despite vertical stratification strengthening, due to increased surface-bottom oxygen concentration gradient associated with increased oxygen release in surface water and exacerbated oxygen consumption in subsurface water.