The Mekong River Basin (MRB) is undergoing unprecedented changes due to the recent acceleration in large-scale dam construction. While the hydrology of the MRB is well understood and the effects of some of the existing dams have been studied, the potential effects of the planned dams on flood pulse dynamics over the entire Lower Mekong remains unexamined. Here, using hydrodynamic model simulations, we show that the effects of flow regulation on downstream river-floodplain dynamics are relatively predictable along the mainstream Mekong, but flow regulations could potentially disrupt the flood dynamics in the Tonle Sap River (TSR) and small distributaries in the Mekong Delta. Results suggest that TSR flow reversal could cease if the Mekong flood pulse is dampened by 50% and delayed by one-month. While flood occurrence in the vicinity of the Tonle Sap Lake and middle reach of the delta could increase due to enhanced low flow, it could decrease by up to five months in other areas due to dampened high flow, particularly during dry years. Further, areas flooded for less than five months and over six months are likely to be impacted significantly by flow regulations, but those flooded for 5-6 months could be impacted the least.