The El Niño–Southern Oscillation (ENSO) responses to global warming has been studied extensively. However, ENSO responds nonlinearly to global warming and may therefore exhibit markedly different behavior at different stages of warming. Understanding these stage-dependent changes is crucial for revealing the physical mechanisms through which global warming affects ENSO and provides insights for interpreting projected ENSO changes during the twenty-first century. Using long-term climate model simulations, we show that ENSO variability exhibits diverse near-term responses but declines robustly under sustained warming beyond 2100. Continued warming raises sea surface temperatures in the eastern equatorial Pacific above the threshold for deep convection, leading to intensified atmospheric convection and a collapse of the mean equatorial upwelling. The combined effects of the upwelling collapse and an increased seawater thermal expansion coefficient weaken the thermocline feedback, while enhanced thermodynamic damping further suppresses ENSO variability. These changes reveal a threshold-like transition in the tropical Pacific climate system: once persistent deep convection develops over the eastern equatorial Pacific, the mean ocean circulation and ENSO dynamics undergo a fundamental reorganization, resulting in a pronounced reduction in ENSO amplitude.