The aim of this study is to look at the impacts of land use and climate change on extreme runoff regimes in selected catchments of Slovakia, with an emphasis on selected characteristics of hydrological regimes, catchment runoff, and, especially extreme runoff. Changing climate conditions, characterized especially by changes in precipitation, air temperatures, and potential evapotranspiration in future decades, have been predicted by recent outputs of the KNMI and MPI regional climate change models and the A1B emission scenario. The land use changes were characterized by various future land use scenarios. Assuming these scenarios are accurate, the hydrological regime characteristics were simulated by the WetSpa distributed rainfall-runoff model, which was parameterized for the selected river basins with a daily time step until 2100. Changes in the total runoff and its components (the maximum and design discharges), as well as changes in soil moisture and actual evapotranspiration, compared to the current state, confirm the assumption of an increase in the extremes of the hydrological regimes during periods of flood events. The results of the study showed a need for a reevaluation of design discharge values for future designs of water management structures.