Natural resources of the Mekong River are essential to livelihood of tens of millions of people. Previous studies highlighted that upstream hydro-infrastructure developments impact flow regime, sediment and nutrient transport, bed and bank stability, fish productivity, biodiversity and biology of the basin. Here, we show that tidal amplification and saline water intrusion in the Mekong Delta develop with alarming paces. While offshore M₂ tidal amplitude increases by 1.2–2 mm yr⁻¹ due to sea level rise, tidal amplitude within the delta is increasing by 2 cm yr⁻¹ and salinity in the channels is increasing by 0.2–0.5 PSU yr⁻¹. We relate these changes to 2–3 m bed level incisions in response to sediment starvation, caused by reduced upstream sediment supply and downstream sand mining, which seems to be four times more than previous estimates. The observed trends cannot be explained by deeper channels due to relative sea level rise; while climate change poses grave natural hazards in the coming decades, anthropogenic forces drive short-term trends that already outstrip climate change effects. Considering the detrimental trends identified, it is imperative that the Mekong basin governments converge to effective transboundary management of the natural resources, before irreversible damage is made to the Mekong and its population.