Drought drastically restricts wheat production, so to dissect allelic variations of drought tolerant genes without imposing trade-offs between tolerance and yield is essential to cope with the circumstance. Here, we identify a drought tolerant WD40 protein encoding gene TaWD40-4B.1 of wheat via the genome-wide association study. The full-length allele TaWD40-4B.1 but not the truncated allele TaWD40-4B.1 possessing a nonsense nucleotide variation enhances drought tolerance and grain yield of wheat under drought. TaWD40-4B.1 interacts with canonical catalases, promotes their oligomerization and activities, and reduces H O levels under drought. The knock-down of catalase genes erases the role of TaWD40-4B.1 in drought tolerance. TaWD40-4B.1 proportion in wheat accessions is negatively correlative with the annual rainfall, suggesting this allele may be selected during wheat breeding. The introgression of TaWD40-4B.1 enhances drought tolerance of the cultivar harboring TaWD40-4B.1 . Therefore, TaWD40-4B.1 could be useful for molecular breeding of drought tolerant wheat.