The ecology of floodplain ecosystems evolved according to the historical frequency and extent of inundation. In many dryland rivers, inundation frequency has reduced due to regulation, competition for water resources and climate change. In some rivers infrastructure has been constructed to enable temporary rises in water level and more frequent floodplain inundation, delivering environmental water to ecosystems that are dependent on surface water. During such events, the release of dissolved organic carbon (DOC) from inundated plant material may result in depletion of dissolved oxygen (DO). If the rate of DO depletion exceeds re‐aeration, hypoxic conditions can occur. Models have been developed to represent these processes, however, there is a wide range of chemical and biological interactions, and hence model parameters, involved. The aim of this research was: (1) identify the dominant parameters through sensitivity analysis, (2) design and implement a field monitoring program to quantify the inherent variability in those parameters, and (3) translate that input variability into the modelled DO, ultimately to support risk management decisions when planning delivery of environmental water. The results indicated that the mass of organic matter on a floodplain had the greatest impact on the modelled DO concentrations. Based on the field monitoring results, the steady state load of organic matter, that is, when the accumulation and decay rates are equal, was estimated, and vegetation mapping used to apply the field monitoring results across the floodplain for a 206 km reach of river of the River Murray, Australia. The model results from multiple, cumulative, operations identified one particular high‐risk operational site. The results are useful to prioritize monitoring effort to focus on the most sensitive model parameters and indicate that the likelihood of hypoxic conditions can be reduced through slower rates of inundation and timing events to coincide with periods with lower water temperature. The methodology developed can be transferred to other sites where hypoxic conditions are a potential outcome associated with delivery of environmental water.