Despite decades of study we have limited insights into the nature of the pre-European landscape of the northeastern USA and the forces and changes that shaped modern forest patterns. Information on such long-term forest dynamics would provide critical insights into the relationships among environmental change, land-use history and biotic responses and is greatly needed for conservation planning. To address these issues we used modern, historical, and paleoecological approaches to reconstruct the 3500-year history of a New England upland region dominated by oak and (formerly) chestnut forests and to interpret the interactions among climate change, natural and human disturbance, and site factors in controlling vegetation patterns and dynamics at different spatial scales. The results indicate that stand, landscape and regional forest dynamics were most strongly driven by climate, notably an apparent cooling and increase in moisture availability c. 1500 yr BP, and European land-use activities commencing 260 yr BP. However, the abundance of oak and chestnut (fire-tolerant, sprouting species) and the distribution of hemlock (fire-intolerant) at a stand to landscape scale were also influenced by fire, which, in turn, varied with climate and human activity. Despite, or perhaps as a consequence of ongoing disturbance by fire and presumably windstorms in this hurricane-prone region, the pre-European period was marked by two 1000+ year periods of remarkably stable forest composition, separated by an abrupt compositional shift. In contrast, over the past 260 years the vegetation has changed rather continuously in response to human activity, producing stand, landscape and regional patterns that are novel as well as recent in origin. Chestnut was a major component of some pre-European landscapes in New England, in part because of occasional fire, and that cultural and physical factors have interacted over millennia to control vegetation patterns and dynamics. Our analyses also suggest that the composition of low diversity forests can be remarkably stable over millennia. The range of ecological, cultural and management insights afforded by this study underscores the fundamental utility of very long-term research in science and policy development.