This study investigates the use of large-scale ensemble weather predictions provided by the National Centers for Environmental Prediction (NCEP) Global Forecast System [GFS; formerly known as Medium-Range Forecast (MRF)] for improving week-2 hydrologic forecasting. The ensemble weather predictor variables are used to downscale daily precipitation and temperature series at two meteorological stations in the Saguenay watershed in northeastern Canada. Three data-driven methods—namely, the statistical downscaling model (SDSM), the time-lagged feed-forward neural network (TLFN), and evolutionary polynomial regression (EPR)—are used as comparative downscaling models. The downscaled results of the best models are used as additional inputs in two hydrological models, namely Hydrologiska Byråns Vattenbalansavdelning (HBV2005) and a Bayesian neural network (BNN)-based hydrologic model, for up to 14-day-ahead reservoir inflow and river flow forecasting. The performance of the two hydrologic models is compared, the ultimate objective being to improve week-2 (7–14-day ahead) forecasts. To identify a suitable approach for using the ensemble weather data in the downscaling experiments, six scenarios are evaluated. It is found that the best approach to downscaling the ensemble weather predictions is to use the means of the predictor members derived from the two grid points closest to the local meteorological station of interest. The downscaling results show that all three models have a relatively good performance in downscaling daily temperature series, but the results are in general less accurate for daily precipitation. The TLFN and EPR models have quite close performance in most cases, and they both perform better than SDSM. The hydrologic forecasting results show that for both reservoir inflow and river flow, the HBV model has better performance when downscaled meteorological predictions are included, while there is no significant improvement for the BNN model. For the week-2 forecast, an improvement of about 18% on average is obtained for both streamflow and reservoir inflow forecasts. However, for the spring season where accurate peak flow forecast is of main concern, an improvement of about 26% on average is achieved. It is also shown that using only downscaled temperature in spring reservoir inflow forecasting, the improvements for week 2 range from 16% to 24%. Overall, the forecast results show that large-scale ensemble weather predictions can be effectively exploited through statistical downscaling tools for improved week-2 hydrologic forecasts. The forecast results also indicate that even imperfect medium-range (week 2) weather predictions can be very useful for producing significantly improved week-2 hydrologic forecasts.