During protracted drought periods in the Murray-Darling Basin, native fish persist in refuge waterholes which can become hypoxic and undergo significant warming. These conditions compromise fish physiological function by simultaneously elevating metabolic demand (warming) and reducing the availability of oxygen (hypoxia) required to fuel aerobic processes. This study investigated whether juvenile golden perch (Macquaria ambigua), could mitigate the deleterious effects of hypoxia and warming through mechanisms of physiological phenotypic plasticity and behavioural changes. Juvenile golden perch were acclimated to either normoxic (100% air saturation) or hypoxic waters (50% air saturation) warmed to 30°C for six weeks. Following acclimation, metabolic physiology, blood oxygen carrying capacity, hypoxia and thermal tolerance and behavioural responses to hypoxia and predation were assessed for both acclimation groups under normoxic and hypoxic conditions. Prolonged exposure to moderate hypoxia improved the overall hypoxia tolerance and additionally produced cross-tolerance to elevated temperatures in golden perch. Physiological plasticity of the heart and spleen also resulted following hypoxia acclimation, with both increasing in size to support an elevated haematocrit. The improved blood-oxygen carrying capacity facilitated the maintenance of aerobic scope in hypoxia-acclimated fish despite conditions of low environmental O2. Fish behaviour was also modulated by hypoxia acclimation, reducing their preference for normoxic environments but not improving their resilience to aerial predators. Golden perch were ultimately capable of adjusting their physiology and behaviour to offset moderate chronic hypoxia stress. The results of this study have implications for developing habitat suitability models to guide the management of crucial waterhole habitat and predict fish-kill risk.