The Mississippi-Atchafalaya River Basin delivers large amounts of freshwater and nutrients to the northern Gulf of Mexico promoting the development of a large hypoxic zone every summer. Statistical and semiempirical models have long been used to provide seasonal forecasts of the mid-summer hypoxic extent using historic time series of spring nutrient load and mid-summer hypoxic extent. These forecasts consist of a scalar estimate of the hypoxic area with uncertainty but do not include spatial distributions or temporal evolution of hypoxic conditions. Three-dimensional (3D) circulation-biogeochemical models of the coastal ocean simulate the temporal evolution of hypoxia in a spatially explicit manner but have not yet been used for seasonal hypoxia forecasting. Here, we present a hybrid method for seasonal, spatially explicit, time-evolving forecasts of the hypoxic zone that combines statistical forecasting with information from a 3D biogeochemical model. The hybrid method uses spring nitrate load and a multiyear (1985-2018) 3D hindcast simulation to produce a seasonal forecast. Validation shows that the method explains up to 76% of the observed year-to-year variability in the hypoxic area. The forecasts suggest that the maximum seasonal extent of hypoxia is reached, on average, on August 13, 2 weeks after the completion of the annual cruise. An analysis of month-to-month variations in hypoxia forecasts due to variability in wind speed and freshwater discharge allows estimates of weather-related uncertainties in the forecast.