Agriculture's need to feed the growing population is challenged by the decline in available water resources especially in the context of global climate change. Improving crop water use efficiency (WUE) will help to safeguard the environmental sustainability of food production in dryland areas. However, the impact of drought on crop WUE varies—a comprehensive and quantitative understanding of relevant factors is needed to support evidence-based management decisions. Here, we used a meta-analysis of global drylands (81 studies with 836 paired observations) to evaluate the response of various crop WUEs to drought based on various natural and human induced factors. Our results showed that responses of crop types’ WUE varied under drought intensity, which probably a reference for crop selection in drylands. Cotton could be one of crop selection reference in hyper-arid or arid regions, and legume is not recommended for drylands without irrigation. Cereal crop are suitable for growing in semi-arid or dry sub-humid areas. Moreover, soil improvement and fertilizer management are the effective methods to alleviate drought stress, in addition to irrigation. Soil with medium-texture, 1.3–1.4 g cm−3 bulk density and 15–20 g kg−1 organic matter is beneficial for improving WUE under drought. Fertilizer should be carefully considered and not exceed 200 kg ha−1 for wheat in drylands. Water deficit can improve crop WUE, but should not exceed 40% of the full irrigation amount. Field management practices, such as mulching and weed control, can help alleviate drought by regulating WUE to some extent. This study evaluated the responses of various crop WUEs to drought and highlighted the factors contributing to and/or decreasing crop WUE from natural factor and management practices, which provides a basis for agricultural drought mitigation strategies under future climate change in dryland areas.