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Vapor pressure deficit (VPD) is a widely used measure of atmospheric water demand. It is closely related to crop evapotranspiration and consequently has major impacts on crop growth and yields. Most previous studies have focused on the impacts of temperature, precipitation, and solar radiation on crop yields, but the impact of VPD is poorly understood. Here, we investigated the spatial and temporal changes in VPD and their impacts on yields of major crops in China from 1980 to 2008. The results showed that VPD during the growing period of rice, maize, and soybean increased by more than 0.10 kPa (10 yr)(-1) in northeastern and southeastern China, although it increased the least during the wheat growing period. Increases in VPD had different impacts on yields for different crops and in different regions. Crop yields generally decreased due to increased VPD, except for wheat in southeastern China. Maize yield was sensitive to VPD in more counties than other crops. Soybean was the most sensitive and rice was the least sensitive to VPD among the major crops. In the past three decades, due to the rising trend in VPD, wheat, maize, and soybean yields declined by more than 10.0% in parts of northeastern China and the North China Plain, while rice yields were little affected. For China as a whole, the trend in VPD during 1980-2008 increased rice yields by 1.32%, but reduced wheat, maize, and soybean yields by 6.02%, 3.19%, and 7.07%, respectively. Maize and soybean in the arid and semi-arid regions in northern China were more sensitive to the increase in VPD. These findings highlight that climate change can affect crop growth and yield through increasing VPD, and water-saving technologies and agronomic management need to be strongly encouraged to adapt to ongoing climate change.