Through water use efficiency (WUE), we can have a deep understanding of the relationship between water and carbon cycles in ecosystems and better assess the responses of ecosystems to climate change. The Yangtze River Economic Zone, with rich natural resources and complex ecosystem patterns, is an important area for economic development and responding to climate change in China. In order to study the changes of WUE and its relationship with temperature and precipitation, an ecosystem process model, Carbon Exchange between Vegetation, Soil and Atmosphere (CEVSA2), was used to estimate the temporal and spatial variation of WUE in the Yangtze River Economic Zone from 1981 to 2010. The evapotranspiration (ET) and net primary productivity (NPP) were obtained by CEVSA2 and the correlation coefficients between annual mean WUE and annual precipitation and mean temperature were calculated. SPSS19, ArcGIS10.2 and Envi 5.3 were used in the analysis. The results showed that: (1) the mean WUE of the Yangtze River Economic Zone from 1981 to 2010 was 1.14 g C mm^-1 m^-2. In spatial distribution, WUE was significantly positive correlated with annual precipitation (r=0.571, P < 0.01), while significantly negative correlated with annual temperature (r=-0.740, P < 0.01). (2) The WUE variation range of the Yangtze River Economic Zone was 1.04-1.19 g C mm^-1 m^-2 during 1981-2010, and the WUE showed a decreasing trend by 0.0030 g C mm^-1 m^-2 a^-1. (3) The WUE of four main vegetation types, including evergreen needle-leaved tree cover, evergreen broadleaved tree cover, herbaceous cover, and evergreen shrub cover, showed a downward trend with rate -3.29×10^-3, -2.99×10^-3, -3.30×10^-3 and -2.65×10^-3 g C mm^-1 m^-2 a^-1, respectively. In 81.58% of the study area (P < 0.05), the WUE was negatively correlated with annual mean temperature between 1981 and 2010, while positively correlated with annual precipitation in 85.92% of the study area (P < 0.05) during the same period. The correlation between WUE and precipitation of all vegetation types was not as significant as that between WUE and temperature. Therefore, the impact of temperature on WUE is greater than precipitation in this study area. In the future, higher spatial resolution and longer time series observation data are needed to simulate the water and carbon cycle and analyze its coupling relationship.