Vegetation restoration is the primary task of ecological reconstruction and rocky desertification control in Karst areas. With vegetation net primary productivity and coverage as two key indicators, a vegetation ecological quality evaluation model was built based on meteorological and remote sensing data. Spatiotemporal variation of vegetation ecological quality index and its response to climate change in rocky desertification areas in Southwest China during 2000–2020 were also analyzed by using the difference method and linear trend method. The results showed that: (1) Vegetation ecological quality in rocky desertification areas in Southwest China showed a fluctuating upward trend during 2000–2020. In 2020, the vegetation ecological quality index reached 69.7, which was 19.9% and 9.3% higher than the averaged values for 2000 and 2000–2019, respectively, ranking the fourth highest since 2000. (2) Vegetation ecological quality of the rocky desertification areas in Yunnan, Guangxi and Guizhou provinces have been improved by 89.2%, 99.2% and 98.5%, respectively, from 2000 to 2020, with their vegetation ecological quality index values increasing by 0.5–0.75 per year in southeast Yunnan, most areas in Guizhou and northwest Guangxi. (3) Precipitation was an important meteorological factor affecting the vegetation ecological quality in rocky desertification areas. The vegetation ecological quality index in the northwest and central Yunnan rocky desertification areas has been rising slowly, but with localized declines at a yearly rate of nearly 0.25 caused by climatic warming and drying.