Lakes hold much of Earth's accessible liquid freshwater, support biodiversity and provide key ecosystem services to people around the world. However, they are vulnerable to climate change, for example through shorter durations of ice cover, or through rising lake surface temperatures. Here we use a one-dimensional, numerical lake model to assess climate change impacts on mixing regimes in 635 lakes worldwide. We run the lake model with input data from four state-of-the-art model projections of 21 st century climate under two emissions scenarios. Under the scenario with higher emissions (Representative Concentration Pathway 6.0), many lakes are projected to have reduced ice cover; about a quarter of seasonally ice-covered lakes are permanently ice-free by 2080-2100. Surface waters are projected to warm, with a median warming across lakes of about 2.5°C, and the most extreme warming at about 5.5°C. The projections suggest that around 100 of the studied lakes are projected to undergo changes in their mixing regimes. About a quarter of these lakes which are currently classified as monomictic-that undergo one mixing event in most years-will become permanently stratified systems. About a sixth of these which are currently dimicticthat mix twice per year-will become monomictic. We conclude that many lakes will mix less frequently in response to climate change. Documented climate-related changes in lakes include shorter durations of winter ice cover 1-4 and higher lake surface temperatures 5-9. Recent global studies of lake surface temperature trends show that many lakes, predominantly those that experience seasonal ice cover, are warming at rates in excess of ambient air temperature 7-8. Studies of lake temperature responses to climate change have improved our understanding of the consequences of warming on lake ecosystems 10, 11. Here, we assess for 635 globally distributed large lakes how projected climate trends are likely to change lake stratification and mixing. Because these aspects of lake dynamics exert significant control on nutrient fluxes, oxygenation and biogeochemical cycling 12, 13 , considering stratification and mixing is critical for anticipating the repercussions of temperature change throughout lake environments and associated ecosystems. Stratification and mixing regimes in lakes Thermal stratification occurs in lakes as a result of the thermal-expansion properties of water. The time evolution of stratification is determined by the balance between turbulence, which acts to enhance mixing, and buoyancy forces, which act to suppress turbulence and result in a