Elevated CO2 (eCO2) has important impacts on plants, especially on water use efficiency (WUE). A meta-analysis was performed to determine the responses of WUE to enriched CO2. We summarized 242 studies on WUE research under ambient and enriched CO2 conditions that were published between 1989 and 2019. Our results showed that WUE had positive responses to elevated CO2 with an increase of about 46% and high heterogeneity. Elevated CO2 increased leaf, grain, biomass and whole plant WUE by 76%, 9%, 30% and 37%, respectively. The effect size on leaf WUE was higher than the other three WUE types, and the effect size on whole plant WUE was higher than grain WUE (P<0.05). In another respect, the response of WUE in forests was higher than in cropland (P<0.05). Regarding different experimental methods, WUE had a stronger response to elevated CO2 by the method of climate-controlled chamber than by the methods of OTC (Open Top Chamber) or greenhouses (P<0.05). However, the effect size obtained by the method of greenhouse was higher than that obtained by the methods of either OTC or climate chamber for whole plant WUE (P<0.05). Furthermore, our results found WUE had a positive linear relationship with the magnitude of CO2 enrichment (P<0.05). Meanwhile, the effect size of elevated CO2 on grain WUE had a positive linear relationship with the duration of CO2 enrichment. This study found that the impacts of CO2 enrichment on WUE are unique and specific for different WUE types and the various experimental conditions.