Groundwater extraction can deplete streamflow in headwater catchments, but the complexity of subsurface hydrological processes make impacts difficult to detect. Using hydrograph-inferred hillslope groundwater storage and streamflow relationships, we propose a novel approach to estimate streamflow depletion from groundwater pumping that is well-suited to areas with limited groundwater monitoring infrastructure. We apply this method in two well-studied watersheds in California’s North Coast to quantify potential hydrologic impacts of cannabis agriculture, which is concentrated in the region and has been identified as a potential threat to salmon-bearing streams. We use a scenario-based approach to explore the relative effects of cannabis cultivation area, irrigation water source (groundwater pumping vs. surface diversion), irrigation efficiency, stream discharge at the onset of the growing season, and lithology on streamflow depletion risk. Our models show that Elder Creek, a perennial stream, could be de-watered by the late dry season with high levels (1% land cover) of cannabis irrigation from groundwater when dry season discharge is low at the start of the season (1 mm/day). In Dry Creek, a nonperennial stream, dry season flow cessation could be advanced by five weeks from similar levels of cannabis water demands. Streamflow impacts are more pronounced in drier years, and the impacts from well-water extraction exhibit a muted effect relative to surface water diversion of the same volume. Storage-discharge functions like those in our case study can estimate how groundwater extraction affects headwater streams wherever streamflow data exist.