The metalimnetic oxygen minimum (MOM) are widely observed in deep lakes and may pose substantial risks to ecosystem stability and key ecological functions. Lake Fuxian, storing nearly 50% of Class I freshwater resources in China, plays a vital role in national water resource security. However, the mechanisms underlying MOM formation in Lake Fuxian and its long-term response to climate warming remain poorly understood. Based on high-frequency monitoring data from 2021 to 2024 and a process-based hydrodynamic-ecological model (GOTM-WET), this study reconstructed the evolution of MOM in Lake Fuxian from 1945 to 2024. Scenario simulations were employed to identify and quantify the major oxygen-consuming processes that drive MOM formation and dynamics. The results showed that MOM had occurred persistently during stratified periods since the 1980s. Relative to 1980, DO concentration within the MOM zone declined at a rate of 0.20 ± 0.03 mg/L/decade, while its occurrence depth shoaled by 0.45 ± 0.21 m/decade and thickness increased by 1.07 ± 0.17 m/decade. The volume proportion of MOM relative to the metalimnion rose by 6.44 ± 0.98 %/decade, and its annual duration extended by 31.20 ± 5.08 days/decade. These long-term trends were significantly correlated with enhanced thermal stratification, including increased Schmidt stability, shallower metalimnion, and longer stratification periods. This suggested that climate warming intensified hypoxia risk by providing more stable and persistent physical conditions for oxygen-consuming biogeochemical processes in the metalimnion. Model results indicated that phytoplankton respiration was the dominant oxygen-consuming pathway in the metalimnion (accounting for 62.7% of total consumption), followed by dissolved organic matter (DOM) mineralization (17.3%), particulate organic matter (POM) mineralization (9.8%), and nitrification (9.3%), with sediment oxygen demand (SOD) contributing the least (0.9%). In the MOM zone, the relative importance of DOM mineralization, POM mineralization, and nitrification increased significantly, contributing 27.5%, 19.7%, and 16.7%, respectively. Scenario analyses further revealed that DOM mineralization and net oxygen consumption by phytoplankton (including both direct metabolism and indirectly induced oxygen-consumption processes) were the primary drivers of MOM formation. Meanwhile, POM mineralization, nitrification, and SOD regulated the intensity, persistence, and vertical distribution of MOM, together forming a critical process network sustaining oxygen depletion in the metalimnion. Overall, this study highlights a coupled physical-biogeochemical mechanism of MOM development in deep lakes under climate warming, whereby enhanced stratification and oxygen-consuming processes jointly drive low-oxygen conditions. These findings provide scientific insights for understanding ecosystem responses in deep lakes to climate change and for formulating effective management strategies.