A better understanding of responses of the regional water-energy cycle to land use/cover change (LUCC) is important for ecological restoration in the agro-pastoral ecotone, Northwest China (APENWC). In this study, we examined the responses to various types of LUCC in the APENWC during the implementation of the Grain-for-Green project between 1993 and 2010 using the weather research and forecasting (WRF) model. The performance of the WRF model was validated by multiple types of observations. Results show that the WRF can accurately simulate regional water and energy processes in the APENWC, and that the water-energy cycles in the region are strongly affected by vegetation dynamics. During the period of 1993 and 2010, the most obviously increased land cover types were the grassland and barren land, and the decreased land cover types were shrublands and croplands in the study region. A significantly negative correlation (R2 = 0.78) between land surface temperature (LST) and albedo was found, associated with a 0.5 °C reduction in the annual mean surface temperature in the APENWC between 1993 and 2010. Negative correlations between changes in evapotranspiration (ET) and albedo during the period in all seasons were also detected, except summer, when the correlation was positive (R2 = 0.49). This is attributed to transpiration from plants being the main contributor to ET in summer and, hence total ET. The changes resulted in an increase of ET by 19.79 mm in summer, and decreases of ET by 1.15 mm, 13.22 mm, and 0.96 mm, respectively, in spring, fall, and winter. The LUCC also resulted in reductions in precipitation (of 2.3, 7.31, and 7.8 mm in spring, summer, and fall, respectively) by altering local ET and vapor flux cycles in the APENWC, and the study region contributed additional moisture from the local ET into the north of the region. The findings show that the grassland expansion reduces mean land surface temperature, which will delay germination of seeds and initiation of vegetation growth in spring. Increases in seasonal ET and reductions in seasonal precipitation will lead to soil drying, exacerbating risks of summer drought in the APENWC. The findings provide important information in facilitating formulation of effective strategies for sustainable development and ecological restoration in the APENWC and similar regions.