Increasing crop productivity under climate change requires the identification, selection and utilization of novel alleles for breeding. We analyzed the genotype and field phenotype of the barley HEB-25 multi-parent mapping population under well-watered and water-limited (WW and WL) environments for two years. A genome-wide association study (GWAS) for genotype by-environment interactions was performed for ten traits including flowering time (HEA) and plant grain yield (PGY). Comparison of the GWAS for traits per-se to that for QTL-by-environment interactions (QxE), indicates the prevalence of QxE mostly for reproductive traits. One QxE locus on chromosome 2, Hordeum spontaneum Dry2.2 (HsDry2.2), showed a positive and conditional effect on PGY and grain number (GN). The wild allele significantly reduced HEA, however this earliness was not conditioned by water deficit. Furthermore, BC2F1 lines segregating for the HsDry2.2 showed the wild allele confers an advantage over the cultivated in PGY, GN and harvest index as well as modified shoot morphology , longer grain filling period and reduced senescence (only under drought), therefore suggesting adaptation mechanism against water deficit other than escape. This study highlights the value of evaluating wild relatives in search of novel alleles and provides clues to resilience mechanism underlying crop adaptation to abiotic stress.