Evapotranspiration (ET), as a crucial component of terrestrial ecosystem carbon and water cycles, plays a significant role in the ecological security and sustainable development of the Huaihe River Eco-Economic Belt (HREB). This strategically important region, spanning China's eastern and central areas, exhibits distinct spatial heterogeneity in its ecological environment. Based on MODIS ET data from 2003 to 2022, this study reveals that ET in the HREB shows a clear spatial pattern of increasing from northeast to southwest, with a significant multi-year average increase of 5.244 mm/year across most regions. Notably, the Hurst exponent analysis predicts a declining ET trend in 63.42% of the area, particularly in the northern semi-arid regions, which warrants special attention in ecological management. Through partial correlation analysis, we found that in this transitional climate zone between north and south China, Leaf Area Index (LAI) and temperature (TEMP) emerge as the dominant factors influencing annual ET variations, affecting 36.8% and 27.3% of the area respectively. Ridge regression further identifies LAI (33.05%), TEMP (25.13%), and surface net thermal radiation (STR) (25.87%) as the primary contributors to interannual ET variations, while precipitation (PRE) shows relatively minor influence (4.91%). These findings not only deepen our understanding of the climate-vegetation-ET interactions in this ecologically vulnerable region but also provide scientific support for formulating regional ecological management strategies and climate adaptation measures, particularly for addressing challenges in water resource management and ecosystem restoration in the HREB.