The Coweeta LTER program consists of multi-scale process-oriented research on the consequences to the southern Appalachian socio-ecological system of the interaction between changing climate and land use. We expect landscapes in the southeastern U.S. to change profoundly in the next five decades as the socioeconomic factors driving the dramatic exurbanization of the past three decades persist, and the changes to the rates, frequencies, and intensities of important climatic factors occur. Climate and land use change will especially impact the rural and quasi-rural lands that still characterize much of southern Appalachia, which is both a ‘water tower’ to the Southeast and one of the most biodiverse temperate regions in the U.S. if not the world. Our research program extends long-term measurements, field experiments and interdisciplinary modeling from small watershed studies to regional-scale analyses so as to account for increases in resource demand and competition from adjacent and more distant areas. Our focus is on the provisioning service of water quantity, the regulating service of water quality, and the supporting service of maintaining biodiversity. The overarching question that guides this research is: How will key ecosystem processes and the focal ecosystem services of water quantity, water quality, and biodiversity be impacted by the: (1) transition in land uses from wildland to urban and peri-urban; (2) changes in climate; and (3) interactions between changes in land use and climate including both on-site and off-site feedbacks? Our research is organized into five components. These are designed to provide critical within-system knowledge across a range of temporal and spatial scales by examining processes associated with (1) Parcel-Level to Regional Decision Making, (2) Longitudinal Variation in Hillslope, Riparian, and Stream Ecology, (3) Impacts of Climate and Land Use Change on Biodiversity and (4) Baseline Data and Temporal Reconstruction. Data and analytical results from each component will be linked through (5) Synthesis & Scaled Integration. The research provides the foundation for comparative analyses, which are increasingly necessary for understanding the local manifestations of global change whether in climate or human settlement, in ways that advance knowledge of complexity about socio-ecological systems.