The mobility and dietary preferences of now-extinct proboscideans have not been comprehensively examined in the central USA. We used stable carbon (δ13C), oxygen (δ18O) and strontium (87Sr/86Sr) isotopic signatures in molar enamel to investigate the foraging ecology of four mastodons (Mammut americanum) and eight mammoths (Mammuthus spp.) from southwestern Ohio and northwestern Kentucky. We tested two hypotheses: (i) these individuals were nomadic migrants that were passing through the region when they died; and (ii) mammoths and mastodons foraged in different environments. Unexpectedly, our results suggest that 11 of the 12 sampled individuals were regional residents. With the exception of one mastodon, 87Sr/86Sr ratios for proboscideans and regional water samples were statistically indistinguishable; slightly lower ratios for waters suggest glacial loess has an impact on modern samples. Amongst the individuals identified as residents, 87Sr/86Sr ratios indicate that mammoths and mastodons foraged in discrete geographical areas, and δ13C values imply dietary differences between the genera, which is consistent with our expectations. Oxygen isotope values may be able to distinguish animals that lived during the Last Glacial Maximum (LGM) from those that lived more recently. Three mammoths and one mastodon yielded δ18O values that are similar to modern regional precipitation and surface water, but too high for estimated drinking water during the LGM. We propose that these individuals lived during a relatively warm period following the LGM. Compellingly, the mammoth with the highest δ18O value also has the lowest δ13C value, suggesting that this individual was alive after regional vegetation shifted from open parkland to deciduous forest dominated by C3 species. Our results demonstrate that a wealth of information can be gleaned from fossil museum specimens and lay a foundation for future work on the foraging ecology of proboscideans and other extinct megafauna from the Midwest USA.