Sediment-laden riverine floods transport large quantities of dissolved oxygen into the receiving deep layers of lakes. Hence, the water quality of deep lakes is strongly influenced by the frequency of riverine floods. Although flood frequency reflects climate conditions, the effects of climate variability on the water quality of deep lakes is largely unknown. We quantified the effects of climate variability on the potential shifts in the flood regime of the Alpine Rhine, the main catchment of Lake Constance, and determined the intrusion depths of riverine density-driven underflows and the subsequent effects on water exchange rates in the lake. A simplified hydrodynamic underflow model was developed and validated with observed river inflow and underflow events. The model was implemented to estimate underflow statistics for different river inflow scenarios. Using this approach, we integrated present and possible future flood frequencies to underflow occurrences and intrusion depths in Lake Constance. The results indicate that more floods will increase the number of underflows and the intensity of deep-water renewal – and consequently will cause higher deep-water dissolved oxygen concentrations. Vice versa, fewer floods weaken deep-water renewal and lead to lower deep-water dissolved oxygen concentrations. Meanwhile, a change from glacial nival regime (present) to a nival pluvial regime (future) is expected to decrease deep-water renewal. While flood frequencies are not expected to change noticeably for the next decades, it is most likely that increased winter discharge and decreased summer discharge will reduce the number of deep density-driven underflows by 10% and favour shallower riverine interflows in the upper hypolimnion. The renewal in the deepest layers is expected to be reduced by nearly 27%. This study underlines potential consequences of climate change on the occurrence of deep river underflows and water residence times in deep lakes.