Wheat was one of the crops domesticated in the Fertile Crescent region approximately 10,000 years ago. Despite undergoing recent polyploidization, hull-to-free-thresh transition events, and domestication bottlenecks, wheat is now grown in over 130 countries and accounts for a quarter of the world’s cereal production. The main reason for its widespread success is its broad genetic diversity that allows it to thrive in different environments. To trace historical selection and hybridization signatures, genome scans were performed on two datasets: approximately 113K SNPs from 921 predominantly bread wheat accessions and approximately 110K SNPs from about 400 wheat accessions representing all ploidy levels. To identify environmental factors associated with the loci, a genome–environment association (GEA) was also performed. The genome scans on both datasets identified a highly differentiated region on chromosome 4A where accessions in the first dataset were dichotomized into a group (n = 691), comprising nearly all cultivars, wild emmer, and most landraces, and a second group (n = 230), dominated by landraces and spelt accessions. The grouping of cultivars is likely linked to their potential ancestor, bread wheat cv. Norin-10. The 4A region harbored important genes involved in adaptations to environmental conditions. The GEA detected loci associated with latitude and temperature. The genetic signatures detected in this study provide insight into the historical selection and hybridization events in the wheat genome that shaped its current genetic structure and facilitated its success in a wide spectrum of environmental conditions. The genome scans and GEA approaches applied in this study can help in screening the germplasm housed in gene banks for breeding, and for conservation purposes.