A new 10-member ensemble simulation with the state-of-the-art Earth system model was employed to study the long-term climate response to sustained greenhouse warming through to the year 2500. The findings show that the projected changes in the forced mean state and internal variability during 2101–2500 differ substantially from the 21st-century projections, emphasizing the importance of multi-century perspectives for understanding future climate change and informing effective mitigation strategies.