We applied an eco-hydrologic model (Regional Hydro-Ecologic Simulation System [RHESSys]), constrained with spatially distributed field measurements, to assess the impacts of forest-fuel treatments and wildfire on hydrologic fluxes in two Sierra Nevada firesheds. Strategically placed fuels treatments were implemented during 2011–2012 in the upper American River in the central Sierra Nevada (43 km2) and in the upper Fresno River in the southern Sierra Nevada (24 km2). This study used the measured vegetation changes from mechanical treatments and modelled vegetation change from wildfire to determine impacts on the water balance. The well-constrained headwater model was transferred to larger catchments based on geologic and hydrologic similarities. Fuels treatments covered 18% of the American and 29% of the Lewis catchment. Averaged over the entire catchment, treatments in the wetter central Sierra Nevada resulted in a relatively light vegetation decrease (8%), leading to a 12% runoff increase, averaged over wet and dry years. Wildfire with and without forest treatments reduced vegetation by 38% and 50% and increased runoff by 55% and 67%, respectively. Treatments in the drier southern Sierra Nevada also reduced the spatially averaged vegetation by 8%, but the runoff response was limited to an increase of less than 3% compared with no treatment. Wildfire following treatments reduced vegetation by 40%, increasing runoff by 13%. Changes to catchment-scale water-balance simulations were more sensitive to canopy cover than to leaf area index, indicating that the pattern as well as amount of vegetation treatment is important to hydrologic response.