Many ecological phenomena combine to direct vegetation trends over time, with climate and disturbance playing prominent roles. To help decipher their relative importance during Euro-American times, we employed a unique approach whereby tree species/genera were partitioned into temperature, shade tolerance, and pyrogenicity classes and applied to comparative tree-census data. Our megadata analysis of 190 datasets determined the relative impacts of climate vs. altered disturbance regimes for various biomes across the eastern United States. As the Euro-American period (ca. 1500 to today) spans two major climatic periods, from Little Ice Age to the Anthropocene, vegetation changes consistent with warming were expected. In most cases, however, European disturbance overrode regional climate, but in a manner that varied across the Tension Zone Line. To the north, intensive and expansive early European disturbance resulted in the ubiquitous loss of conifers and large increases of Acer, Populus, and Quercus in northern hardwoods, whereas to the south, these disturbances perpetuated the dominance of Quercus in central hardwoods. Acer increases and associated mesophication in Quercus-Pinus systems were delayed until mid 20th century fire suppression. This led to significant warm to cool shifts in temperature class where cool-adapted Acer saccharum increased and temperature neutral changes where warm-adapted Acer rubrum increased. In both cases, these shifts were attributed to fire suppression rather than climate change. Because mesophication is ongoing, eastern US forests formed during the catastrophic disturbance era followed by fire suppression will remain in climate disequilibrium into the foreseeable future. Overall, the results of our study suggest that altered disturbance regimes rather than climate had the greatest influence on vegetation composition and dynamics in the eastern United States over multiple centuries. Land-use change often trumped or negated the impacts of warming climate, and needs greater recognition in climate change discussions, scenarios, and model interpretations.