Wheat is the most widely grown staple crop globally. Being largely rain-fed, drought is the main constraint for wheat production accounting for more than half yield loss due to abiotic stress. Wheat is particularly susceptible to water deficit at the jointing stage. Sucrose non-fermenting 1-related protein kinase 2 (SnRK2) acts as a signaling hub of various biological processes and in the response to drought stress, but whether SnRK2 employs other mechanisms to cope with drought stress is largely unknown. Here, we cloned and characterized TaSnRK2.10, which was induced by multiple abiotic stress and phytohormones. Extopic-expression of TaSnRK2.10 conferred pronouncedly enhanced tolerance to severe drought stress, manifested by multiple improved physiological indices, including high water contents, cell membrane stability (CMS) and survival rates, less accumulation of H2O2 and malonaldehyde (MDA), and reduced water loss rates. Moreover, TaSnRK2.10 interacted with and phosphorylated TaERD15 and TaENO1 in vivo and/or in vitro. The phosphorylated TaERD15 by TaSnRK2.10 was prone to be degraded by the 26S proteasome, and thus mitigated its negative effects to drought tolerance. The phosphorylation of TaENO1 by TaSnRK2.10 might increase its catalytic activity, verified by remarkable accumulation of phosphoenolpyruvate (PEP), a key metabolite of primary and secondary metabolisms, thereby enhancing the viability of TaSnRK2.10 transgenic plants under drought stress. Collectively, TaSnRK2.10 not only regulated stomatal aperture and expression of drought-responsive genes, but also enhanced PEP supply by phosphorylation of TaENO1 and promoted the degradation of TaERD15 to reduce its negative effects on drought stress, therefore enhancing drought tolerance.