The Irtysh River Basin (IRB), a transboundary river basin spanning China, Kazakhstan, and Russia, has experienced significant vegetation changes driven by climate change and human activities. This study investigated the spatiotemporal dynamics of different types of vegetation in the IRB from 2001 to 2020 using the normalized difference vegetation index (NDVI) and quantified the contributions of driving forces to the evolution of vegetation. The results revealed that the end of the global warming hiatus in 2013 aggravated climate changes, leading to an abrupt shift in NDVI dynamics. This spatial shift was mainly reflected in grassland and farmland in the arid regions of northern Kazakhstan, where overall vegetation cover has improved in recent years. Precipitation and temperature were identified as the main drivers of spatial vegetation differentiation in the basin, with precipitation being more limiting in arid regions, while temperature affected non-arid regions at higher latitudes more strongly, and climate change had a greater positive effect on vegetation in non-arid regions than in arid regions. The relative contribution of climatic factors to vegetation changes decreased from 45.93% before the abrupt change to 42.65% after the abrupt change, while the contribution of other drivers, including human activities, increased from 54.07% to 57.35%. The combined effect of climate change and human activities was more significant than that of individual drivers, with human interventions such as environmental policies and ecological restoration projects having strongly contributed to the greening trend in recent years. This study highlights the need for zonal management strategies in the IRB, prioritizing sustainable forest management in non-arid zones and sustaining environmental protection projects in arid regions to support vegetation restoration and sustainable ecosystem management.