Background: As an important class of E3 ubiquitin ligases in the ubiquitin proteasome pathway, proteins containing homologous E6-AP carboxyl terminus (HECT) domains are crucial for growth, development, metabolism, and abiotic and biotic stress responses in plants. However, little is known about HECT genes in wheat (Triticum aestivum L.), one of the most important global crops. Methods: Using a genome-wide analysis of high-quality wheat genome sequences, we identified 25 HECT genes classified into six groups based on the phylogenetic relationship among wheat, rice, and Arabidopsis thaliana. Results: The predicted HECT genes were distributed evenly in 17 of 21 chromosomes of the three wheat subgenomes. Twenty-one of these genes were hypothesized to be segmental duplication genes, indicating that segmental duplication was significantly associated with the expansion of the wheat HECT gene family. The Ka/Ks ratios of the segmental duplication of these genes were less than 1, suggesting purifying selection within the gene family. The expression profile analysis revealed that the 25 wheat HECT genes were differentially expressed in 15 tissues, and genes in Group II, IV, and VI (UPL8, UPL6, UPL3) were highly expressed in roots, stems, and spikes. This study contributes to further the functional analysis of the HECT gene family in wheat.