The spatial variability of snow water equivalent (SWE) can exert a strong influence on the timing and magnitude of snowmelt delivery to a watershed. Therefore, the representation of subgrid or subwatershed snow variability in hydrologic models is important for accurately simulating snowmelt dynamics and runoff response. The U.S. Geological Survey National Hydrologic Model infrastructure with the Precipitation-Runoff Modeling System (NHM-PRMS) represents the subgrid variability of SWE with snow depletion curves (SDCs), which relate snow-covered area to watershed-average SWE during the snowmelt period. The main objective of this research was to evaluate the sensitivity of simulated runoff to SDC representation within the NHM-PRMS across the continental United States (CONUS). SDCs for the model experiment were derived assuming a range of SWE coefficient of variation (CV) values and a lognormal probability distribution function. The NHM-PRMS was simulated at a daily time step for each SDC over a 14-year period. Results highlight that increasing the subgrid snow variability (by changing the SDC) resulted in a consistently slower snowmelt rate and longer snowmelt duration when averaged across the hydrologic response unit scale. Simulated runoff was also found to be sensitive to SDC representation, as increases in the subgrid SWE CV by 1.0 resulted in decreases in runoff ratio by as much as 12 percent in snow-dominated regions of the CONUS. Simulated decreases in runoff associated with slower snowmelt rates were approximately inversely proportional to increases in simulated evapotranspiration. High snow persistence and peak SWE:annual precipitation combined with a water limited dryness index were associated with the greatest runoff sensitivity to changing snowmelt. Results from this study highlight the importance of carefully parameterizing SDCs for hydrologic modeling. Furthermore, improving model representation of snowmelt input variability and its relation to runoff generation processes is shown to be an important consideration for future modeling applications.