Barley (Hordeum vulgare L.) is one of the Neolithic founder crops of the early agricultural societies. The circumstances of its domestication and the genomic signatures that underlie barley transition from a weed to a crop remain obscure. We explored genomic variation in a diversity set of 433 wild and domesticated barley accessions using targeted re-sequencing that generated a genome-wide panel of 544,318 high-quality SNPs. We observed a ~50% reduction of genetic diversity in domesticated compared to wild barley and diversity patterns indicative of a strong domestication bottleneck. Selection scans discovered multiple selective sweep regions associated with domestication. The top candidate domestication genes were homologs of the genes, in other plant species, implicated in the regulation of light signaling, the circadian clock, hormone, and carbohydrate metabolism. Phylogeographic analyses revealed a mosaic ancestry of the domestication-related loci, which originated from wild barley populations from both the eastern and western parts of the Fertile Crescent. This indicates that assembly of the mosaic of the cultivated barley genomes was part of the domestication process, which supports a protracted domestication model.