Oxygen depletion constitutes a major threat to lake ecosystems and the services they provide. Most of the world’s lakes are located >45° N, where accelerated climate warming and elevated carbon loads might severely increase the risk of hypoxia, but this has not been systematically examined. Here analysis of 2.6 million water quality observations from 8,288 lakes shows that between 1960 and 2022, most northern lakes experienced rapid deoxygenation strongly linked to climate-driven prolongation of summer stratification. Oxygen levels deteriorated most in small lakes (<10 ha) owing to their greater volumetric oxygen demand and surface warming rates, while the largest lakes gained oxygen under minimal stratification changes and improved aeration at spring overturns. Seasonal oxygen consumption rates declined, despite widespread browning. Proliferating anoxia enhanced seasonal internal loading of C, P and N but depleted P long-term, indicating that deoxygenation can exhaust redox-sensitive fractions of sediment nutrient reservoirs.