Synthetic hexaploid wheat and their advanced derivatives (SYN-DERs) are promising sources for introducing novel genetic diversity to develop climate-resilient cultivars. In a series of field and laboratory experiments, we measured biochemical, physiological and agronomic traits in a diversity panel of SYN-DERs evaluated under well-watered (WW) and water-limited (WL) conditions. ANOVA revealed significant differences among genotypes, treatments and their interaction for all agronomic and physiological traits. The major flowering time determinant gene Ppd-D1 was fixed in diversity panel with presence of photo-period insensitive allele (Ppd-D1a) in 99% accessions. Wild-type alleles at Rht-B1 and Rht-D1, and presence of rye translocation (1B.1R) favored GY in WL conditions. Synthetic hexaploid wheats are one of the most exploited genetic resources for bread wheat improvement. However, despite some QTL with major effects, much less is known about genome-wide patterns of introgressions and their effects on phenotypes. We used two genome-wide association approaches; SNP-GWAS and haplotype-GWAS to identify SNPs and haplotypes associated with productivity under water-limited conditions in a synthetic-derived wheat (SYN-DER) population. Haplotype-GWAS proved to be more powerful and identified 20 genomic regions associated with drought adaptability that did not overlap with SNP-GWAS. These approaches consistently pinpointed 89 „selective sweeps‟, out of which 30 selection loci were identified on D-genome. Our results demonstrated that haplotype-GWAS and selective sweeps are powerful approaches for investigating favorable introgressions and genomic regions under strong selection pressure through the breeding continuum and the use of crop-wild hybridization to assist the improvement of wheat yield and productivity under moisture limiting environments. This study showed sufficient genetic variation in the SYN-DERs diversity panel to improve yields during droughts due to better adaptability than bread wheat.