Purpose: Salinity stress (SS) is a major problem that adversely affects crop growth and productivity across the globe. Acetic acid (AA) has emerged as an essential chemical to induce plant stress tolerance. However, the role of AA in plants under SS is not well explored. Therefore, the present study was conducted to determine the effect of AA on growth, yield, ionic homeostasis, physiology, hormonal crosstalk, and antioxidant activities of wheat crop grown under SS. The study comprised different levels of SS (control [0 dS m−1], 7 dS m−1, and 14 dS m−1) and foliar spray of AA (control [water spray], 10 mM, and 20 mM). SS was imposed by mixing the salt into soil, whereas foliar application of AA was performed at the flag leaf stage. The results indicated that SS stress negatively affected the growth and yield of wheat crop by stimulating oxidative stress, which was associated with H2O2 (39.83%), malondialdehyde (MDA; 26.89%), and abscisic acid (ABA; 33.90%) accumulation; electrolyte leakage (EL; 54.70%); Na+ accumulation; and reduced gas exchange characteristics (photosynthetic rate, transpiration rate, stomatal conductance, and water-use efficiency [WUE]), relative water content (RWC; 34.53%), chlorophyll content, free amino acids (FAA; 32.38%), total soluble protein (TSP; 50.30%), indole acetic acid (IAA; 42.13%), gibberellic acid (GA), and nutrient uptake. However, foliar application of AA significantly improved the growth and yield of wheat crops owing to decreased MDA, H2O2, and ABA accumulation as well as EL. Acetic acid increased RWC, chlorophyll content, anthocyanin content, proline, soluble sugars TSP, FAA, IAA, GA, and the rate of photosynthesis and transpiration, plant WUE, and antioxidant activities (ascorbate peroxidase, catalase, peroxidase, and superoxide dismutase). In addition, application of AA reduced the massive entry of toxic ions (Na+ and Cl−) while it increased the uptake of Ca2+, K+, Mg2+, N, and P, thus improved wheat growth and yield. These findings suggest that AA could mitigate SS in wheat crop by regulating K+ accumulation, gas exchange characteristics, and promoting the scavenging of reactive oxygen species by activating the antioxidant defense system and improving the synthesis and signaling of stress-protection hormones and osmolytes.