Episodic hypoxic events can occur following summer floods in sub-tropical estuaries of eastern Australia. These events can cause deoxygenation of waterways and extensive fish mortality. Here, we present a conceptual model that links key landscape drivers and biogeochemical processes which contribute to post-flood hypoxic events. The model provides a framework for examining the nature of anthropogenic forcing. Modification of estuarine floodplain surface hydrology through the construction of extensive drainage networks emerges as a major contributing factor to increasing the frequency, magnitude and duration of hypoxic events. Forcing occurs in two main ways. Firstly, artificial drainage of backswamp wetlands initiates drier conditions which cause a shift in vegetation assemblages from wetland-dominant species to dryland-dominant species. These species, which currently dominate the floodplain, are largely intolerant of inundation and provide abundant labile substrate for decomposition following flood events. Decomposition of this labile carbon pool consumes oxygen in the overlying floodwaters, and results in anoxic conditions and waters with excess deoxygenation potential (DOP). Carbon metabolism can be strongly coupled with microbially-mediated reduction of accumulated Fe and Mn oxides, phases which are common on these coastal floodplain landscapes. Secondly, artificial drainage enhances discharge rates during the flood recession phase. Drains transport deoxygenated high DOP floodwaters rapidly from backswamp wetlands to the main river channel to further consume oxygen. This process effectively displaces the natural carbon metabolism processes from floodplain wetlands to the main channel. Management options to reduce the impacts of post-flood hypoxia include i) remodifying drainage on the floodplain to promote wetter conditions, thereby shifting vegetation assemblages towards inundation-tolerant species, and ii) strategic retention of floodwaters in the backswamp wetlands to reduce the volume and rate during the critical post-flood recession phase.