• The Tonle Sap is the largest wetland and fishery in the Mekong but it is expected to be affected by hydropower and climate change • Landscape-scale spatial distribution of habitats were found to be largely driven by flood duration patterns. • The flood-pulse hydrology could explain most of the underlying variability in soil and vegetation field-scale characteristics. • Hydropower could cause distinct seasonal changes, while climate change could increase inter-annual uncertainty. • Fauna species richness was found to be greatest in natural habitats likely to experience the most significant disruptions