California has experienced increased drought frequency and intensity in addition to anthropogenic shifts in land use over the past 120 years. We used stable isotope analysis of California voles (Microtus californicus) from museum collections to assess relationships between isotopic composition of vole tissues and known patterns of drought and agricultural intensification. By associating δ15N values of dated hair tissue with monthly statewide drought metrics, we observed a direct relationship between δ15N values and drought intensity. Geospatial patterns of δ34S values of hair tissue reflects baseline isotopic enrichment of coastal habitats with marine-derived sulfate inputs. However, comparably enriched δ34S values in the southern-most inland localities appear to reflect anthropogenic effects on sulfur cycling via sulfur fertilization of croplands and subsequent sulfur transfer offsite in dissolved oxidized and isotopically enriched forms. Stable isotope analysis of museum specimens can thereby provide a climate record based on physiological performance of a study species in a region affected intensely by anthropogenic activities. To follow up such findings, a fine scale analysis of isotopic changes in modern populations over time and over varied climatic conditions is desirable.