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Environmental stresses, especially heat and drought, severely limit plant growth and negatively affect wheat yield and quality worldwide. Heat shock factors (Hsfs) play a central role in regulating plant responses to various stresses. In this study, the wheat heat shock factor gene <i>TaHsfA2e-5D</i> on chromosome 5D was isolated and functionally characterized, with the goal of investigating its role in responses to heat and drought stresses. Gene expression profiling showed that <i>TaHsfA2e-5D</i> was expressed constitutively in various wheat tissues, most highly in roots at the reproductive stage. The expression of <i>TaHsfA2e-5D</i> was highly up-regulated in wheat seedlings by heat, cold, drought, high salinity, and multiple phytohormones. The TaHsfA2e-5D protein was localized in the nucleus and showed a transcriptional activation activity. Ectopic expression of the <i>TaHsfA2e-5D</i> in yeast exhibited improved thermotolerance. Overexpression of the <i>TaHsfA2e-5D</i> in <i>Arabidopsis</i> results in enhanced tolerance to heat and drought stresses. Furthermore, RT-qPCR analyses revealed that <i>TaHsfA2e-5D</i> functions through increasing the expression of Hsp genes and other stress-related genes, including <i>APX2</i> and <i>GolS1</i>. Collectively, these results suggest that <i>TaHsfA2e-5D</i> functions as a positive regulator of plants’ responses to heat and drought stresses, which may be of great significance for understanding and improving environmental stress tolerance in crops.