Previous research has documented declines in the abundance of high-return resources including tule elk (Cervus canadensis nannodes) over the past three millennia in central California, suggesting the occurrence of resource depression. We test the hypothesis that hunting depressed tule elk in this setting by articulating stable isotope analyses from 88 directly dated tule elk specimens with data on the age structure and skeletal part representation from the King Brown and Emeryville Shellmound sites. Late Holocene trends in stable isotopes and modeled climatic variation are inconsistent with climate-based population declines. However, at King Brown, located within the Central Valley and vast tule elk freshwater marsh and grassland habitat, increasing isotopic diversity, a decline in mean age, and increasing abundance of high-utility skeletal elements suggest local depression stimulated the increasing use of distant elk patches. Although faunal trends are consistent with the depression of elk at Emeryville, the site is located on the shore of the San Francisco Bay where limited elk habitat existed, and no evidence of distant elk patch use is indicated. This analysis underscores how human behavioral responses to resource depression can vary in relation to the local ecology as they affect patch use economics for specific prey and demonstrates how such responses can be deciphered through stable isotope and faunal data.