Neogene cooling and aridification in the Northern Hemisphere have long been recognized, but there are no studies comparing patterns of aridity gradients or differences between North America and Eurasia. Large herbivorous mammals are an excellent source for understanding large-scale environmental and climatic patterns because their molar crown height (hypsodonty) reflects both habitat and precipitation. The temporal development of hypsodonty in the North American Great Plains is well studied, but both spatial detail and comparisons with patterns in Eurasia are lacking. Here we use a methodology based on community levels of hypsodonty to estimate precipitation during the Neogene (the past 23 Ma). We show that aridification was more profound and occurred ∼5 Ma earlier in North America than in Eurasia. By combining our results with existing climate model output and new sensitivity experiments, we show how these changes were influenced by ocean heat transport and atmospheric circulation patterns. We further suggest that asymmetric dispersal of large mammals between Eurasia and North America was related to the contrasting humidity regimes between the continents.