Recurring drying and wetting events are likely to increase in frequency and intensity in predicted future droughts in the central United States and alter the regeneration potential of species. We explored the resistance of seed banks to successive droughts in 53 sites across the nine locations in baldcypress swamps in the southeastern United States. Along the Mississippi River Alluvial Valley and northern Gulf of Mexico, we investigated the capacity of seed banks to retain viable seeds after successive periods of drying and wetting in a greenhouse study. Mean differences of species richness and seed density were compared to examine the interactions of successive droughts, geographical location and water regime. The results showed that both species richness and total density of germinating seedlings decreased over repeated drought trials. These responses were more pronounced in geographical areas with higher annual mean temperature. In seed banks across the southeastern swamp region regions, most species were exhausted after Trial 2 or 3, except for semi-aquatic species in Illinois and Tennessee, and aquatic species in Texas. Distinct geographical trends in seed bank resistance to drought demonstrate that climate-induced drying of baldcypress swamps could influence the regeneration of species differently across their ranges. Despite the health of adult individuals, lack of regeneration may push ecosystems into a relict status. Seed bank depletion by germination without replenishment may be a major conservation threat in a future with recurring droughts far less severe than megadrought. Nevertheless, the protection of moist refugia might aid conservation.