Objectives. To comparatively analyze three genomic sequences of Mycobacterium tuberculosis (MTB), including sensitive (INS-SEN), multi-drug-resistant (INS-MDR), and extremely drug-resistant (INS-XDR) strains, collected in Lima, Peru. Materials and Methods. Specific single nucleotide polymorphisms (SNPs) were identified in the INS SEN, INSMDR, and INS-XDR strains according to the inclusion/exclusion criteria. The three MTB genomes were compared and a molecular phylogeny was constructed with 27 MTB strains from other studies available from the Genbank database. Results. The specific SNPs in each genome were organized in clusters of orthologous groups (COGs). The genomic analysis allowed for the identification of a set of SNPs associated mainly with virulence determinants (family of mce proteins, polyketides, phiRv1, transposase, and methyltransferases, and other related to vitamin synthesis). A close correlation between the INS-MDR and INS-XDR strains was observed, with only a 6.1% difference in SNPs; however, the INS-SEN strain had 50.2% and 50.3% different SNPs from the MDR and XDR strains, respectively. The molecular phylogeny grouped the Peruvian strains within the LAM lineage and closely to the F11 and KZN strains from South Africa. Conclusions. High similarity (99.9%) was noted between the INS-SEN strain and the F11 South African strain with broad global scope, while the analysis of the INS-MDR and INS-XDR strains showed a likely expansion of the KZN family, a South African strain with high virulence and pathogenicity.