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Long‐term patterns of dissolved oxygen (DO) in estuarine and coastal waters remain poorly understood. Here we summarized DO concentrations and analyzed the crucial drivers of hypoxia in northwestern and southern Hong Kong and Mirs Bay over the past three decades. Deoxygenation was weak in the bottom water in northwestern Hong Kong, although DO was consistently undersaturated, whereas the annual minimum DO in the bottom water exhibited a significant decrease in southern Hong Kong (−0.06 ± 0.01 mg L−1 yr−1) and Mirs Bay (−0.10 ± 0.02 mg L−1 yr−1). Seasonal hypoxia in the bottom water was accompanied by supersaturated DO and high Chl‐a in surface waters of southern Hong Kong, indicating a crucial role of local extensive productivity in the oxygen depletion of the bottom water. The rapid deoxygenation was also attributed to the water stratification preventing oxygen replenishment in southern Hong Kong and the predeoxygenation of bottom water retained in Mirs Bay. The dissolved inorganic nitrogen concentrations have increased from 1 to 3 mg N L−1, which increased the primary productivity contributing to the decrease in water DO over the past three decades. Therefore, these results suggest that biological oxygen consumption and seasonal stratification are mainly driving the formation and maintenance of hypoxia in the Pearl River Estuary and adjacent areas. Plain Language Summary: We compared dissolved oxygen (DO) concentrations and the driving factors of hypoxia between northwestern and southern Hong Kong and Mirs Bay. Deoxygenation was weak in the bottom layer in northwestern Hong Kong, although the DO was consistently undersaturated, whereas a rapid decrease in the annual minimum DO was observed in the bottom layer in southern Hong Kong and Mirs Bay. The seasonal DO depletion and/or hypoxia in the bottom water was accompanied by supersaturated DO and high Chl‐a in surface water in southern Hong Kong, indicating local excessive productivity in triggering oxygen depletion. The predeoxygenation of bottom water and long water residence time have contributed to the deoxygenation in Mirs Bay. Water stratification could exacerbate hypoxia by preventing oxygen replenishment from the surface to the bottom layers. The upwelling water from the South China Sea and/or Kuroshio contributed inappreciably to the significant deoxygenation in southern Hong Kong and Mirs Bay. These results suggest that enhanced productivity and oxygen consumption, combined with stratification and currents, are increasingly driving hypoxia in the Pearl River Estuary and adjacent areas. Key Points: Nutrients, physical and biological factors affected seasonal fluctuation of DO around Hong Kong watersThe annual minimum dissolved oxygen has declined over a period of 30 yearsMirs Bay will become a potential zone of hypoxia in the Pearl River Estuary [ABSTRACT FROM AUTHOR]