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<i>Staphylococcus aureus</i> (<i>S. aureus</i>) ST22 is considered a clinically important clone because an epidemic strain EMRSA-15 belongs to ST22, and several outbreaks of this clone have been documented worldwide. We performed genomic analysis of an <i>S. aureus</i> strain Lr2 ST22 from Pakistan and determined comparative analysis with other ST22 strains. The genomic data show that Lr2 belongs to <i>spa</i>-type t2986 and harbors staphylococcal cassette chromosome <i>mec</i> (SCC<i>mec</i>) type IVa(2B), one complete plasmid, and seven prophages or prophage-like elements. The strain harbors several prophage-associated virulence factors, including Panton–Valentine leukocidin (PVL) and toxic shock syndrome toxin (TSST). The single nucleotide polymorphism (SNPs)-based phylogenetic relationship inferred from whole genome and core genome revealed that strain Lr2 exhibits the nearest identities to a South African community-acquired methicillin-resistant <i>S. aureus</i> (CA-MRSA) ST22 strain and makes a separate clade with an Indian CA-MRSA ST22 strain. Although most ST22 strains carry <i>blaZ</i>, <i>mecA</i>, and mutations in <i>gyrA</i>, the Lr2 strain does not have the <i>blaZ</i> gene but, unlike other ST22 strains, carries the antibiotic resistance genes <i>erm(C)</i> and <i>aac(6′)-Ie-aph(2″)-Ia</i>. Among ST22 strains analyzed, only the strain Lr2 possesses both PVL and TSST genes. The functional annotation of genes unique to Lr2 revealed that mobilome is the third-largest Cluster of Orthologous Genes (COGs) category, which encodes genes associated with prophages and transposons. This possibly makes methicillin-resistant <i>S. aureus</i> (MRSA) Lr2 ST22 strain highly virulent, and this study would improve the knowledge of MRSA ST22 strains in Pakistan. However, further studies are needed on a large collection of MRSA to comprehend the genomic epidemiology and evolution of this clone in Pakistan.