Abstract: The vegetation distribution map shows the growth state of the vegetation population and is an important indicator for assessing the quality of local ecology. In order to protect the environment, it is very important to explore the vegetation changes in the Huaihe ecological economic belt and the associated climate drivers. Based on time series data and normalised vegetation index (NDVI) meteorological data from 2000 to 2020, this study analyzed the spatio-temporal trends and abrupt changes of climate in the Huaihe River Ecological Economic Belt. Using wavelet analysis, spatial autocorrelation analysis, Sen+Mann-Kendal trend analysis, partial correlation analysis and geographical detector, this paper studied the spatio-temporal evolution of vegetation coverage in Huaihe River ecological economic Belt. The results showed that: (1) From 2000 to 2020, the vegetation area demonstrated a variable growth trend, with the average annual vegetation area of 0.754 and a reduction from southwest to east. (2) The vegetation cover level was relatively high on the whole, and the vegetation cover improvement area was larger than the degraded area in the three different stages from 2000 to 2010, 2010 to 2020 and 2000 to 2020, accounting for 89%, 44.25% and 71.6%, respectively. It was mainly distributed in Xinyang City and Zhumadian City of Henan Province, northern Anhui Province and northern Jiangsu Province. (3) The climate environment in the study area showed a gradual tend to warm and humid between 21a and 21a. The positive correlation between vegetation coverage and precipitation was higher than between relative humidity, temperature and solar radiation. The partial correlation between vegetation coverage and climate factors varied significantly between the regions. (4) The interaction of each driving factor in the region was significantly higher than that of a single driving factor, and most of them showed a nonlinear enhancement trend. The interaction of precipitation was the largest.