Reconstructing water availability in terrestrial ecosystems is key to understanding past climate and landscapes, but there are few proxies for aridity that are available for use at terrestrial sites across the Cenozoic. The isotopic composition of tooth enamel is widely used as a paleoenvironmental indicator and recent work suggests the potential for using the triple oxygen isotopic composition of the carbonate component of mammalian tooth enamel (Δ′17Oenamel) as an indicator of aridity. However, the extent to which Δ′17Oenamel values vary across environments is unknown and there is no framework for evaluating past aridity using Δ′17Oenamel data. Here we present Δ′17Oenamel and δ18Oenamel values from 50 extant mammalian herbivores that vary in physiology, behavior, diet, and water-use strategy. Teeth are from sites in Africa, Europe, and North America and represent a range of environments (humid to arid) and latitudes (34°S to 69°N), where mean annual δ18O values of meteoric water range from –26.0‰ to 2.2‰ (VSMOW). Δ′17Oenamel values from these sites span 162 per meg (–252 to –90 per meg), where 1 per meg = 0.001‰). The observed variation in Δ′17Oenamel values increases with aridity, forming a wedge-shaped pattern in a plot of aridity index vs. Δ′17Oenamel that persists regardless of geographic region. In contrast, the plot of aridity index vs. δ18Oenamel for these same samples does not yield a distinct pattern. We use these new Δ′17Oenamel data from extant teeth to provide guidelines for using Δ′17Oenamel data from fossil teeth to assess and classify the aridity of past environments. Δ′17Oenamel values from the fossil record have the potential to be a widely used proxy for aridity without the limitations inherent to approaches that use δ18Oenamel values alone. In addition, the data presented here have implications for how Δ′17Oenamel values of large mammalian herbivores can be used in evaluations of diagenesis and past pCO2 and past gross primary productivity.