The role of tropical cyclones (TCs) in the water budget of 3211 watersheds in the southeast United States (SE US) over the last decade (2002–2011) is examined in detail at daily and longer time-scales towards mapping regional hydro-climatic vulnerabilities. The work documents highly heterogeneous spatial and inter-annual patterns of variability in the contribution of TC events to the annual cycle of rainfall from below 5% (e.g. 2011) to 65–70% (e.g. 2004 and 2005) at the watershed scale. The data indicate that, with average return periods of 1–3 years, singular TCs are key agents of drought demise redressing watershed precipitation deficits by 30–100%, and a key mechanism of regional meteorological drought mitigation at seasonal and inter-annual time-scales. Flood response and drought mitigation impacts of TCs are stronger for storms with terrestrial tracks predominantly on the Atlantic region and, or aligned with the Appalachian Mountains (AM) where orographic effects are evident in high precipitation amounts and high runoff ratios. Locally, rainfall-runoff response along the terrestrial tracks of TCs increases when inter-storm arrivals are short (<2 weeks), but evidence of the cumulative impact of antecedent precipitation on available soil moisture storage capacity at the seasonal scale is lacking except where groundwater-tables are shallow in the Piedmont and in the Coastal Plain. Flood peaks do not exceed the 2-year flood magnitude event at over 90% of gauged locations for any one storm. Thus, whereas increases in intensity and frequency of TCs should have a positive impact on regional water resources by reducing or interrupting and eliminating severe drought, especially in the Piedmont and Coastal Plains, the impact on river discharge should mostly affect the magnitude of the bank-full and low hydroperiodicity flooding (≤5-year events) that are tightly linked to the functional resiliency of natural and developed landscapes.