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Wheat (Triticum aestivum L.) is one of the most significant cereal crops grown in the semi-arid and temperate regions of the world, but few studies comprehensively explore how the environment affects wheat yield and protein content response to drought by means of meta-analysis. Therefore, we collected data about grain yield (GY), grain protein yield (GPY), grain protein content (GPC), and grain nitrogen content (GNC), and conducted a meta-analysis on 48 previously published data sets that originate from 15 countries. Our results showed that drought significantly decreased GY and GPY by 57.32 and 46.04%, but significantly increased GPC and GNC by 9.38 and 9.27%, respectively. The responses of wheat GY and GNC to drought were mainly related to the drought type, while the GPY was mainly related to the precipitation. The yield reduction due to continuous drought stress (CD, 83.60%) was significantly greater than that of terminal drought stress (TD, 26.43%). The relationship between the precipitation and GPY increased in accordance with linear functions, and this negative drought effect was completely eliminated when the precipitation was more than 513 mm. Sandy soils and high nitrogen application level significantly mitigated the negative effects of drought, but was not the main factor affecting the drought response of wheat. Compared with spring wheat, the drought resistance effect of winter wheat was more obvious. Evaluation of these models can improve our quantitative understanding of drought on wheat yield and food security, minimizing the negative impact of drought on crop production.