Seasonal ice in lakes plays an important role for local communities and lake ecosystems. Here we use Large Ensemble simulations conducted with the Community Earth System Model version 2, which includes a lake simulator, to quantify the response of lake ice to greenhouse warming and to determine emergence patterns of anthropogenic lake ice loss. Our model simulations show that the average duration of ice coverage and maximum ice thickness are projected to decrease over the next 80 years by 38 days and 0.23 m, respectively. In the Canadian Arctic, lake ice loss is accelerated by the cold-season polar amplification. Lake ice on the Tibetan Plateau decreases rapidly due to a combination of strong insolation forcing and ice-albedo feedbacks. Comparing the anthropogenic signal with natural variability represented by the Large Ensemble, we find that lake ecosystems in these regions may be exposed to no-analogue ice coverage within the next 4-5 decades.