During the summers of 2009 and 2013, seawater pH and concentrations of dissolved oxygen, inorganic carbon, and nutrients were measured off the Changjiang estuary in the East China Sea. The 2009 cruise captured the effects of Typhoon Morakot; the 2013 cruise sampled more typical conditions (no typhoon). Data from both years indicate a close correlation between high primary productivity in surface waters and hypoxia in bottom waters. Based on these observations, we developed a conceptual model to guide an exploration of processes contributing to the formation of summertime bottom hypoxia. A mixing-model analysis of the 2009 data identified a surface diatom bloom as the major (70–80%) source of the organic carbon that decomposed and ultimately led to bottom water hypoxia. Within the Changjiang River plume, depth-integrated net biological production in the water column was 1.8 g C m−2 d−1, indicating strong autotrophic production, which in turn led to a high respiration rate of 1.2 g C m−2 d−1 in the bottom water. During both cruises, strong surface-to-bottom physical and metabolic coupling was evident. In 2009, storm-driven inputs of nutrients from elevated river discharge and strong vertical mixing helped to fuel the rapid development of a surface diatom bloom. Afterwards, stratified conditions re-established, newly formed labile organic matter sank, and bottom water oxygen was quickly consumed to an extent that hypoxia and acidification developed. To our knowledge, the observed rate of hypoxia and acidification development (within 6 d) is the fastest yet reported for the Changjiang River plume.