BackgroundClimate change is an important factor driving vegetation changes in arid areas. Identifying the sensitivity of vegetation to climate variability is crucial for developing sustainable ecosystem management strategies. The Irtysh River is located in the westerly partition of China, and its vegetation cover is more sensitive to climate change. However, previous studies rarely studied the changes in the vegetation coverage of the Irtysh River and its sensitivity to climate factors from a spatiotemporal perspective.MethodsWe adopted a vegetation sensitivity index based on remote sensing datasets of high temporal resolution to study the sensitivity of vegetation to climatic factors in the Irtysh River basin, then reveal the driving mechanism of vegetation cover change.ResultsThe results show that 88.09% of vegetated pixels show an increasing trend in vegetation coverage, and the sensitivity of vegetation to climate change presents spatial heterogeneity. Sensitivity of vegetation increases with the increase of coverage. Temperate steppe in the northern mountain and herbaceous swamp and broadleaf forest in the river valley, where the normalized difference vegetation index is the highest, show the strongest sensitivity, while the desert steppe in the northern plain, where the NDVI is the lowest, shows the strongest memory effect (or the strongest resilience). Relatively, the northern part of this area is more affected by a combination of precipitation and temperature, while the southern plains dominated by desert steppe are more sensitive to precipitation. The central river valley dominated by herbaceous swamp is more sensitive to temperature-vegetation dryness index. This study underscores that the sensitivity of vegetation cover to climate change is spatially differentiated at the regional scale.