||A panel of 387 durum wheat genotypes including Mediterranean landraces and modern cultivars was characterized with 46,161 diversity arrays technology (DArTseq) markers. Analysis of population structure uncovered the existence of five subpopulations (SP) related to the pattern of migration of durum wheat from the domestication area to the west of the Mediterranean basin (SPs 1, 2, and 3) and further improved germplasm (SPs 4 and 5). The total genetic diversity (HT) was 0.40 with a genetic differentiation (GST) of 0.08 and a mean gene flow among SPs of 6.02. The lowest gene flow was detected between SP 1 (presumably the ancient genetic pool of the panel) and SPs 4 and 5. However, gene flow from SP 2 to modern cultivars was much higher. The highest gene flow was detected between SP 3 (western Mediterranean germplasm) and SP 5 (North American and European cultivars). A genome wide association study (GWAS) approach using the top ten eigenvectors as phenotypic data revealed the presence of 89 selective sweeps, represented as quantitative trait loci (QTL) hotspots, widely distributed across the durum wheat genome. A principal component analysis (PCoA) using 147 markers with −log10p > 5 identified three regions located on chromosomes 2A, 2B and 3A as the main drivers for differentiation of Mediterranean landraces. Gene flow between SPs offers clues regarding the putative use of Mediterranean old durum germplasm by the breeding programs represented in the structure analysis. EigenGWAS identified selective sweeps among landraces and modern cultivars. The analysis of the corresponding genomic regions in the ‘Zavitan’, ‘Svevo’ and ‘Chinese Spring’ genomes discovered the presence of important functional genes including Ppd, Vrn, Rht, and gene models involved in important biological processes including LRR-RLK, MADS-box, NAC, and F-box.