Global climate change exerts a profound influence on regional vegetation dynamics. Investigating the spatial and temporal variations of the normalized difference vegetation index (NDVI) within watersheds and its responses to climate change is essential for supporting the development and management of regional ecological environments. This study analyzed spatial and temporal variations of NDVI during the vegetation growing season in Inner Mongolia, along with its responses to climate change, using slope analysis and correlation analysis. The study utilized monthly NDVI composite products from MODIS and meteorological data spanning 1999 to 2019. The key findings are: Inner Mongolia’s spatial distribution of average NDVI values exhibited a distinct pattern, with values decreasing progressively from northeast to southwest. During the study period, the mean NDVI values in Inner Mongolia during the growing season demonstrated a significant upward trend, with an average annual increase of 0.0016. Over the 21-year period, temperature trends in Inner Mongolia remained relatively stable, whereas precipitation showed a significant increasing trend. The correlation between vegetation NDVI and climatic factors during the growing season varied significantly across regions. Precipitation was found to have a stronger and more consistent influence on vegetation growth compared to temperature, underscoring its pivotal role in the region. The interannual shift in the center of gravity of average NDVI values was minimal, predominantly confined to northeastern Inner Mongolia. These findings offer a valuable scientific basis for Inner Mongolia’s ecological environment protection and restoration efforts.