Global warming decreases the solubility of oxygen in seawater and increases the biogeochemical oxygen consumption in the water column, leading to the potential for further hypoxia. The effects of environmental factors such as climatic mixing and nutrient loads from rivers on the expansion of hypoxic water vary according to regional characteristics. A previous study based on a deterministic approach reported the earlier onset and expansion of hypoxia in Osaka Bay, a hypoxic coastal sea in Japan. However, the influences of river discharge and wind conditions on currents, density distributions, and hypoxia formation in the bay are highly variable. Deterministic experiments fall short in evaluating these future changes and their associated uncertainties. The objective of this study is to evaluate the effects of uncertainties in climate model predictions on the prediction of hypoxia in Osaka Bay. We discuss changes in the spatial distribution of hypoxic water and the meteorological factors that contribute to these changes based on three-dimensional hydrodynamic and biogeochemical simulations using multiple forecast meteorological datasets. The simulations used Regional Ocean Modeling Systems (ROMS) and a nitrogen-based biogeochemical model. To consider climate model uncertainties, 30 ensembles of present and future scenarios were randomly selected from the product of super-ensemble simulations, which contained downscaling experiments using six models. The simulation results showed a trend of early hypoxia expansion in the warming scenario, including variations in the meteorological field and freshwater inflow. In the future ensembles, the variance from the mean volumes of the simulated hypoxia was approximately 0.6 km3 on average over the computation period. The model estimated that the hypoxic volume decreased when the mean temperature increased in August. However, the differences in mean discharge did not show a clear correlation with the magnitude of hypoxia. Analysis of the simulated oxygen distribution suggested that hypoxia was most pronounced around August in the current scenario. Contrastingly, in the warmer future scenario, concentrations of dissolved oxygen remained low near the bottom but were higher in the middle depths in comparison to the present ensembles.