Wheat is susceptible to atmospheric ozone (O3) pollution, thus the increasing O3 is a serious threat to wheat production. γ-aminobutyric acid (GABA) is found to play key roles in the tolerance of plants to stress. However, few studies elaborated the function of GABA in response of wheat to O3. Here, we incorporate metabolome and transcriptome data to provide a more comprehensive insight on the role of GABA in enhancing the O3-tolerance of wheat. In our study, there were 31, 23, and 32 differentially accumulated flavonoids in the carbon-filtered air with GABA, elevated O3 with or without GABA treatments compared to the carbon-filtered air treatment, respectively. Elevated O3 triggered the accumulation of dihydroflavone, flavonols, and flavanols. Exogenous GABA enhanced dihydroflavone and dihydroflavonol, and also altered the expression of genes encoding some key enzymes in the flavonoid synthesis pathway. Additionally, GABA stimulated proline accumulation and antioxidant enzyme activities under elevated O3, resulting in the less accumulation of H2O2 and malondialdehyde. Consequently, GABA alleviated the grain yield loss from 19.6% to 9.6% induced by elevated O3. Our study provided comprehensive insight into the role of GABA in the alleviating the detrimental effects of elevated O3 on wheat, and a new way to mitigate O3 damage to the productivity of crops. Tropospheric ozone (O3) in the atmosphere is one of major air pollutants and has strong oxidizability, imposing serious threat to human health and plants. With a progressive increase in its concentrations in many regions, its ecologically hazardous effects on plants are becoming more and more of a concern. As one of the most important staple crops, wheat is susceptible to O3 pollution. In the present study, we investigated whether γ-aminobutyric acid can alleviate the O3-induced detriment to wheat. Our study provides a new method to remove the hazardous effects of O3 on plants.