Lakes on the Tibetan Plateau are expanding rapidly in response to climate change. The potential impact on the local environment if lake expansion continues remains uncertain. Here we integrate field surveys, remote sensing observations and numerical modelling to assess future changes in lake surface area, water level and water volume. We also assess the ensuing risks to critical infrastructure, human settlements and key ecosystem components. Our results suggest that by 2100, even under a low-emissions scenario, the surface area of endorheic lakes on the Tibetan Plateau will increase by over 50% (~20,000 km2) and water levels will rise by around 10 m relative to 2020. This expansion represents approximately a fourfold increase in water storage compared with the period from the 1970s to 2020. A shift from lake shrinkage to expansion was projected in the southern plateau around 2021. The expansion is primarily fuelled by amplified lake water inputs from increased precipitation and glacier meltwater, profoundly reshaping the hydrological connectivity of the lake basins. In the absence of hazard mitigation measures, lake expansion is projected to submerge critical human infrastructure, including more than 1,000 km of roads, approximately 500 settlements and around 10,000 km2 of ecological components such as grasslands, wetlands and croplands. Our study highlights the urgent need for water hazard mitigation and management across the Tibetan Plateau.