Taking the South China karst as an example, this study constructed compound use efficiency (COM) through water, light, and carbon use efficiency (WUE, LUE, and CUE), analysed the divergence characteristics of COM, and clarified the dominant factor of COM variation and their sensitivity. It showed that from 2000 to 2018, WUE, LUE, CUE, and COM showed significant nonlinear characteristics; spatially, which were distributed in a “northeast-southwest” pattern. Different factors on COM exhibited significant spatial heterogeneity. The COM first stabilized and then exhibited a fluctuating decrease with rising elevation and slope. The COM increased sharply and then slightly decreased as the temperature and precipitation increased but decreased with enhanced solar radiation and human activity intensity (HAI). HAI had the greatest effect on COM change, and the COM-HAI sensitivity first decreased and then increased, 2006 was the abrupt year, this may be related to the time-lagged effect of ecological restoration on vegetation.