The principal aims of this study were to explore genetic diversity and genome-wide selection signatures in Persian Arabian horses and to determine genetic relationship of Persian Arabians with other Iranian horse breeds. We evaluated 71 horses from 8 matrilineal strains tracing to 47 mares from the mid to late 19th century, using the equine 670k SNP BeadChip. Mean observed and expected heterozygosity were (0.43) and (0.45), respectively, average inbreeding measures (FROH and FPED) were low, indicating high genetic diversity in Persian Arabian horses. Analysis of population genetic structure using STRUCTURE and Principal Component Analysis suggested that Persian Arabian horses can be divided into three groups, however the groups do not match traditional matrilineal strains. In total, 15 genomic regions were identified by at least two of the three implemented methods, Tajima’s D, H, and H12, as potentially under selection in Persian Arabian horses. Most of these peaks were found on chromosome 9, overlapping with QTLs previously associated with horse temperament. Biological function analysis of identified candidate genes highlighted enrichment of GO term “response to lipopolysaccharide” and KEGG pathway “chemokine-mediated signaling pathway”, which are associated with immune responses and may have been targets of selection in Persian Arabian horses. Independent analyses of SNP data from 30 horses of four other Iranian breeds suggested distinct population structure between Persian Arabian, and Turkemen and Caspian horse breeds. Overall, the results of this study suggest a rich genetic diversity in the Persian Arabian horses and a clear genetic differentiation with Turkemen and Caspian breeds.