Deoxygenation has frequently appeared in coastal ecosystems over the past century due to the joint influence of increasing anthropogenically induced nutrient inputs and global warming. The semi-enclosed Bohai Sea is a typical system that is prone to deoxygenation, with regular hypoxia events consistently recorded in recent decades. Based on in-situ observation data collected in large-scale voyage surveys in the Bohai Sea during 2008–2017, the seasonal variability in dissolved oxygen (DO) and its controlling mechanisms were studied. The results indicated that in spring and autumn, the DO distributions exhibited similar spatial patterns in the surface and bottom layers, while in summer, its spatial distribution was characterized by large-scale oxygen-poor zones distributed offthe Qinhuangdao Coast and the central southern Bohai Sea in the bottom layer. The controlling mechanisms of the DO distribution varied from season to season. Spring and autumn DO distributions were dominated by the seawater temperature. Under the combined effects of stratification and decomposition, the summer bottom DO exhibited dual-core distribution. On the one hand, stratification could greatly impede vertical mixing, resulting in reduced bottom DO replenishment. On the other hand, the increased bottom organic matter intensified the decomposition processes, inducing massive DO consumption and elevated dissolved inorganic nitrogen concentrations. In addition, the stronger stratification might be the reason for the more severe deoxygenation in the southern oxygen-poor zones in summer. Our study provides guidance for an in-depth understanding of the DO seasonality in the Bohai Sea and the mechanisms that modulate it and for the improvement of hypoxia forecasts in ocean models.