It is crucial to determine the factors affecting the carbon use efficiency (CUE) and water use efficiency (WUE) of vegetation in ecosystems. However, the relationships between climate changes and CUE and WUE by karst vegetation in China are still unclear. The response of the CUE and WUE to regional climate change was studied by using trend analysis and partial derivative method. In addition, the distribution characteristics of the CUE and WUE of different land use types were analyzed. The following results were found. (1). From 2000 to 2018, the average of CUE in karst areas of China was 0.557, and the average value of WUE was 1.237g C kg−1 H2O. (2) The CUE of grassland was higher than that of forest land (0.051), whereas the WUE value of grassland was far lower than that of forest land (1.415 g C kg−1 H2O). (3) CUE was affected by precipitation (P), exhibiting an increasing trend (5.5 × 10−3 yr−1), and the most obvious increase occurred in the grassland (7.2 × 10−3 yr−1). Under the influence of solar radiation (SR), the WUE decreased (−1.5 × 10−3 g C kg−1 H2O yr−1), and the largest decrease occurred in the shrub land (−8.4 × 10−3 g C kg−1 H2O yr−1). (4) 90.31 % CUE increase depended on P and SR, while 78.32 % of the decrease in the WUE was due to P and SR. This study makes important contributions to clarifying the responses of the CUE and WUE of ecosystems to climate changes in karst areas, optimizing the management of regional water and soil resources, and promoting healthy development of the ecological environment.