Understanding streamflow dynamics in watersheds affected by human activity and climate variability is important for sustainable water and environmental resource management. This study evaluates the vulnerability of Alabama watersheds to anthropogenic and climatic changes using an integrated framework combining GIS, remote sensing, hydrological modeling, and machine learning (ML). Three Soil and Water Assessment Tool (SWAT) models, differing in spatial resolution and soil inputs, were developed to simulate streamflow under baseline and land-use/land cover (LULC) scenarios from 1990 to 2023. The model, built with consistent 100 × 100 m rasters and fine-resolution SSURGO (Soil Survey Geographic Database) soil data, achieved the best calibration and was selected for detailed analysis. Streamflow trends were assessed over two periods (1993–2009 and 2010–2023) to help isolate climate variability (from LULC effects), while LULC changes were evaluated using 1992, 2011, and 2021 maps. A Long Short-Term Memory (LSTM) model further enhanced simulation accuracy by integrating partially calibrated SWAT outputs. Watershed vulnerability was ranked using a multi-criteria framework. Two watersheds were classified as highly vulnerable, nine as moderately vulnerable, and three as having low vulnerability. Basin-level contrasts revealed moderate climate impacts in the Tombigbee Basin, greater climate sensitivity in the Black Warrior Basin, and LULC-dominated impacts in the Alabama Basin. Overall, LULC change exerted stronger and more spatially variable effects on streamflow than climate variability. This study introduces a transferable SWAT–ML vulnerability ranking framework to guide watershed and environmental management in data-scarce, human-modified regions.