Vegetation Carbon Use Efficiency (CUE) and Water Use Efficiency (WUE) are key indicators for revealing the coupled processes of ecosystem carbon and water cycles. Based on MODIS remote sensing data from 2000 to 2020 and relying on the Google Earth Engine platform, combined with trend analysis, coefficient of variation, rescaled range (R/S) analysis, and partial correlation methods, this study explored the spatiotemporal evolution characteristics of vegetation CUE and WUE in the Huaihe River Ecological Economic Belt and their response mechanisms to climatic factors. The results showed that: (1) the annual mean values of CUE and WUE in the study area were 0.51 and 0.75 gC·m-2·mm-1, respectively. CUE exhibited a fluctuating downward trend overall, while WUE showed a fluctuating upward trend. Spatially, CUE presented a pattern of being higher in the east and lower in the west, while high-value areas of WUE were similar to those of CUE, and low-value areas were mainly distributed in the central-northern and central-southern parts; (2) trend analysis indicated that the proportion of areas with improved WUE (32.91%) was significantly higher than that of CUE (13.87%). R/S analysis predicted that in the future, 63.41% of the area would show a positive development trend for CUE, while the proportion of positive development areas for WUE was 36.43%; (3) climate factor response analysis revealed that CUE was negatively correlated with temperature and sunshine duration, but positively correlated with precipitation and soil moisture. In contrast, WUE was positively correlated with temperature, but negatively correlated with precipitation, sunshine duration, and soil moisture, with precipitation and temperature showing significant spatial heterogeneity in their effects. This study reveals the nonlinear response mechanisms of vegetation carbon and water use efficiency to climatic factors in the subtropical–warm temperate transition zone, providing theoretical support for regional ecological function optimization and the realization of the “dual carbon” goals.