Potential vegetation succession processes in the Heihe River watershed were simulated over a 50 year period from 1961 to 2010 using integrated sequence classification. The simulation was supported by GIS information and climate data from 14 weather stations covering this time period. Linking the dynamic response of vegetation to climate change was achieved by analyzing the potential ecological environment changes in the Heihe River watershed under different climate conditions. The results show that: 1) Potential vegetation types gradually reduced in the Heihe River watershed with only 11 types remaining by the 1991 to 2010 period, and with significant differences in spatial distribution. 2) In the upper and middle reaches of the Heihe River watershed the climate is predicted to become wetter and warmer and the potential vegetation influence indicates a change toward warm and wet adapted species but with a more rapid change to warm than wet adapted species. In contrast, the climate becomes drier and warmer with a corresponding change in the potential vegetation type to warm and dry in the downstream mesozoic-cenozoic region, aggravating desertification. 3) As the climate changes, vegetation types gradually reduce in the entire drainage basin and the potential ecological damage increases. Climate change and human factors have resulted in serious deterioration of the ecological environment in downstream mesozoic-cenozoic areas.