Climate change significantly affects growth status of vegetation in arid and semi-arid zones, and it is crucial to recognize temporal effects of climate on vegetation growth. The ignorance of temporal effects could lead to bias in attributing vegetation dynamics. In the study, the Theil-Sen Median trend and Mann-Kendall test methods were combined to show the trend of NDVI during the growing season between 2001 and 2020 in the Irtysh River Basin. Multiple linear regression model was used to explore the temporal effects of climate change on vegetation. Then, improved residual analysis considering the time effect was applied to quantify the contribution of climate change and human activities to NDVI changes. The results were as follows: 1) NDVI in the Irtysh River Basin has been increasing at a rate of 0.0017/a for the last two decades, with growth rates of 0.0019/a, 0.0014/a, and 0.0068/a for grasslands, forests, and wetlands, respectively; 2) the impact of precipitation on vegetation had an average lag of 1.92 months, with average cumulative of 1.90 months, while the impact of temperature on vegetation had an average lag of 1.70 months, with average cumulative of 1.57 months; 3) After considering the time effect, the average explanatory ability of climate change to NDVI changes increased by 7.84%, with an overall contribution of 29.27%; 4) increased precipitation and glacial melting due to warmer temperatures in the Altai Mountains promoted vegetation growth, while reduced precipitation and increased evaporation in the south desert regions inhibited vegetation growth. The study can provide data base and scientific support for the ecological conservation of the Irtysh River Basin by exploring the interrelationships between vegetation dynamics and climate change while taking time effect into consideration.