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The effects of global climate change are manifested at the regional level; consequently, evaluation of links between palaeoenvironmental change and turnover of past biotas must use regional-scale climate data. Here we test whether climate change influenced faunal and floral patterns leading up to, and during, the mid-Miocene Climatic Optimum (MMCO) based on datasets collected in the Railroad Canyon section (RCS), central-eastern Idaho, U.S.A. Specifically, we use isotope compositions of herbivore tooth enamel to investigate how Mean Annual Precipitation (MAP), Mean Annual Temperature (MAT), Cold Month Mean Temperature (CMMT), and temperature seasonality varied through the RCS and how this local record compares to global climate reconstructions. Isotope compositions of teeth from the fossil equid Merychippus and rhinocerotid Diceratherium were compared across five time bins from c. 23 to c. 15 Ma. Bulk δ18O values of both taxa indicate that meteoric water compositions were unchanged through the study interval (consistently c. −15.6‰) but were c. 1.9‰ higher than current regional meteoric water. This difference points to warmer climates in central-eastern Idaho during the Miocene, post-middle Miocene topographic uplift in western North America, and/or shifts to air mass trajectories. Serial sampling of enamel shows seasonal fluctuations in water compositions and temperature. Bulk δ13C values indicate an average MAP of 190 (range: 10–510 mm·yr−1), with no significant change through the study interval, comparable to today's MAP (236 mm·yr−1). The reconstructed semi-arid, seasonal, warm climate for the RCS agrees with phytolith assemblage data from the same strata indicating dominantly open, grassy habitats. However, it is inconsistent with previously held ideas of warm-wet mid-Miocene climates in the northern Rocky Mountains (NRM) based on paleosol analyses. Our inferred, stable climate conditions for the MMCO of the NRM contrast with coeval records from Europe and Asia indicating sustained or enhanced warm and wet climates. These differences point to a decoupling of regional climate from global trends and highlight the necessity of studying regional variation to understand the biotic impacts of global climate change.