Increasing occurrence of large and severe wildfires represents a growing threat to forested watersheds and the many ecosystem services they provide. Past research has shown that wildfires can cause substantial increases in peak flows and annual water yields, leading to potential water quality concerns and land and water management challenges. However, responses have been variable, and there have been few studies at large basin scales, leading to uncertainties about post-fire hydrologic responses. To address these uncertainties, we projected the effect of three large wildfires (>70,000 ha) on streamflow in two important forested watersheds in the Cascade Range of Oregon, US. We modeled the streamflow response using the Soil and Water Assessment Tool (SWAT) model, calibrated on data from prior to the wildfires. We modified model parameters to represent the impacts of the wildfires based on burn severity maps. Burned and unburned scenarios were compared using random forest models to identify drivers of increased annual water yields and peak flows. Post-fire annual water yield changes were controlled by burn severity, annual precipitation, area burned, aridity, and vegetation type, while post-fire peak flow changes were controlled by burn severity, area burned, aridity, soil type, and geologic province. We also found that post-fire increases in annual water yields, peak flows, and low flows were greatest at the headwater scale but were more muted at the downstream basin scale. Our work provides valuable insights into the range of potential post-fire streamflow changes at the headwater and larger basin scale, which is becoming increasingly critical for effective forest and water management decisions.