The hydrological regime of the Rhine basin is expected to shift from a combined snowmelt-rainfall regime to a more rainfall-dominated regime because of climate change, leading to more extreme flood peaks and low flows. Land use changes may reinforce the effects of this shift through urbanization or may counteract them through, for example, afforestation. In this study, we investigate the effect of projected land use change scenarios on river discharge. Sensitivity of mean and extreme discharge in the Rhine basin to land use changes is investigated at various spatial scales. The variable infiltration capacity (VIC) (version 4.0.5) model is used for hydrological modeling forced by a high-resolution atmospheric data set spanning the period 1993–2003. The model is modified to allow for bare soil evaporation and canopy evapotranspiration simultaneously in sparsely vegetated areas, as this is more appropriate for simulating seasonal effects. All projected land use change scenarios lead to an increase in streamflow. The magnitude of the increase, however, varies among subbasins of different scales from about 2% in the upstream part of the Rhine (about 60,000 km2) to about 30% in the Lahn basin (about 7000 km2). Streamflow at the basin outlet proved rather insensitive to land use changes because over the entire basin affected areas are relatively small. Moreover, projected land use changes (urbanization and conversion of cropland into (semi)natural land or forest) have opposite effects. At smaller scales, however, the effects can be considerable.