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Streamflow is one the most important variables controlling and maintaining aquatic ecosystem integrity, diversity, and sustainability. This study identified and quantified changes in 34 hydrologic characteristics and parameters at 30 long term discharge stations in the Southeast Atlantic and Gulf Coast Hydrologic Region (Region 3) using Indicators of Hydrologic Alteration (IHA) variables. The southeastern United States (SEUS) is a biodiversity hotspot, and the region has experienced a number of rapid land use/land cover changes with multiple primary drivers. Studies in the SEUS have been mostly localized on specific rivers, reservoir catchments and/or species, but the overall region has not been assessed for the long-term period of 1939-2016 for multiple hydrologic characteristic parameters. The objectives of the study were to provide an overview of multiple river basins and 31 hydrologic characteristic parameters of streamflow in Region 3 for a longer period and to develop a conceptual map of impacts of selected stressors and changes in hydrology and climate in the SEUS. A seven step procedure was used to accomplish these objectively:Step 1: Download data from the 30 USGS gauging stations. Steps 2 and 3: Select and analyze the 31 IHA parameters using boxplots, scatter plots, and PDFs. Steps 4 and 5: Synthesize the drivers of changes and alterations and the various change points in streamflow in the literature.Step 6: Synthesize the climate of the SEUS in terms of temperature and precipitation changes.Step 7: Develop a conceptual map of impacts of selected stressors on hydrology using Driver-Pressure-State-Impact-Response (DPSIR) framework and IHA parameters. The 31 IHA parameters were analyzed. The meta-analysis of literature in the SEUS revealed the precipitation changes observed ranged from −30% to +35% and temperature changes from −2 • C to 6 • C by 2099. The fiftieth percentile of the Global Climate Models (GCM) predict no precipitation change and an increase in the temperature of 2.5 • C in the region by 2099. Among the GCMs, the 5th and 95th percentile of precipitation changes range between −40% and 110% and temperature changes between −2 • C and 6 • C by 2099. Meta-analysis of land use/land cover show the region has experienced changes. A number of rapid land use/land cover changes in 1957, 1970, and 1998 are some of the change points documented in the literature for precipitation and streamflow in the region. A conceptual map was developed to represent the impacts of selected drivers and the changes in hydrology and climate in the study region for three land use/land cover categories in three different periods.